Targeting Delivery Research Articles

Target-Specific Delivery and Bioavailability of Pharmaceuticals via Janus and Dendrimer Particles.

Nanosized Janus and dendrimer particles have emerged as promising nanocarriers for the target-specific delivery and improved bioavailability of pharmaceuticals. Janus particles, with two distinct regions exhibiting different physical and chemical properties, provide a unique platform for the simultaneous delivery of multiple drugs or tissue-specific targeting. Conversely, dendrimers are branched, nanoscale polymers with well-defined surface functionalities that can be designed for improved drug targeting and release. Both Janus particles and dendrimers have demonstrated their potential to improve the solubility and stability of poorly water-soluble drugs, increase the intracellular uptake of drugs, and reduce their toxicity by controlling the release rate. The surface functionalities of these nanocarriers can be tailored to specific targets, such as overexpressed receptors on cancer cells, leading to enhanced drug efficacy The design of these nanocarriers can be optimized by tuning the size, shape, and surface functionalities, among other parameters. The incorporation of Janus and dendrimer particles into composite materials to create hybrid systems for enhancing drug delivery, leveraging the unique properties and functionalities of both materials, can offer promising outcomes. Nanosized Janus and dendrimer particles hold great promise for the delivery and improved bioavailability of pharmaceuticals. Further research is required to optimize these nanocarriers and bring them to the clinical setting to treat various diseases. This article discusses various nanosized Janus and dendrimer particles for target-specific delivery and bioavailability of pharmaceuticals. In addition, the development of Janus-dendrimer hybrid nanoparticles to address some limitations of standalone nanosized Janus and dendrimer particles is discussed.

Current Strategies for Exosome Cargo Loading and Targeting Delivery

Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention as promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer and are secreted by various cells. Due to their high biocompatibility, stability, and low immunogenicity, exosomes are favored as cargo carriers. The lipid bilayer membrane of exosomes also offers protection against cargo degradation, making them a desirable candidate for drug delivery. However, loading cargo into exosomes remains to be a challenge. Despite various strategies such as incubation, electroporation, sonication, extrusion, freeze–thaw cycling, and transfection that have been developed to facilitate cargo loading, inadequate efficiency still persists. This review offers an overview of current cargo delivery strategies using exosomes and summarizes recent approaches for loading small-molecule, nucleic acid, and protein drugs into exosomes. With insights from these studies, we provide ideas for more efficient and effective delivery of drug molecules by using exosomes.

Biomimetic Nanoparticles for Cancer Targeting and Drug Delivery

0Cellular membrane engineered nanoparticles (NPs) have shown immense potential for anti-cancer drug delivery applications. In principle, cell membrane of any type of cells can be processed to obtain purified cellular membrane which can self-assemble to form stable and highly robust nanovesicles. These nanovesicles retain lipid-bilayer architecture of host’s cells and much of the surface biomarkers and proteins are conserved during top-down approach. Interestingly, nanovesicles have exhibited long plasma circulation and appreciable tumour specific binding, which is largely suggestive of their biomimetic properties. Many pioneer studies have demonstrated their ability to encapsulate different chemotherapeutic agents and photosensitizers of varied chemical complexities, and releasing them in a triggered fashion. Additionally, the novel NPs system has been developed for cancer immunotherapy. The review discusses some of the important research and applications of cellular membrane derived nanovesicles for different forms of cancer therapy and their potential to be developed as personalized nanomedicine.

Advances of Chitin Biomass Derived from Seafood Waste in Biomedical Applications

As the second abundant biomass in nature, chitin widely exists in crustaceans, insects, plankton, fungi and so on. Thus, extracting chitin from crustaceans’ seafood waste and applying it and its derivatives in biomedicine represents the idea of turning waste into treasure. However, the poor solubility severely limits the application range and field of chitin. Thus, the chemical modification of chitin has always been a hot field in the research of such compounds, endowing chitin better solubility, pH-sensitive targeting, and drug delivery functions. In this review, the modification methods of chitin were summarized to improve the water solubility, pH sensitivity and targeting of chitin derivatives. At the same time, the application of chitin derivatives in many fields such as antibacterial, sustained release, targeting and drug delivery are introduced. This review offers a good reference for sustainable development.

O021 Utilising an accelerated delphi process to develop consensus on the requirement and components of a pre-procedural core robotic surgery curriculum

Abstract Introduction Robot-assisted Surgery (RAS) continues to grow globally. Despite this, in the UK and Ireland, it is estimated that over 70% of surgical trainees across all specialities have no access to robot-assisted surgical training (RAST). This study aimed to provide educational bodies guidance on a pre-procedural core robotic surgery curriculum (PPCRC) from the perspective of the end user; the surgical trainee. Methods The study was conducted in four Phases: P1: A steering group was formed and a systematic review conducted P2: Pan-Specialty Trainee Panel Virtual Classroom Discussion, P3: Accelerated Delphi Process and P4: Formulation of Recommendations. Forty-three surgeons in training representing all surgical specialties and training levels contributed to a three-round Delphi process. Additions to the second- and third-round surveys were formulated based on the answers and comments from previous rounds. Consensus opinion was defined as ≥80% agreement. Results There was 100% response from all three rounds. The formulated guidance showed good internal consistency (Cronbach alpha >0.8). There was 97.7% agreement that a standardised PPCRC would be advantageous to training and that, independent of speciality, there should be a common approach (95.5% agreement). Consensus was reached in multiple areas: 1. Experience and Exposure, 2. Access and context, 3. Curriculum Components, 4 Target Groups and Delivery, 5. Objective Metrics, Benchmarking and Assessment. Conclusion Using accelerated Delphi methodology, multispecialty consensus among trainees to develop and reach content validation for the requirements and components of a PPCRC in the UK and Ireland was achieved. This guidance will benefit from further validation following implementation.

Platelet Membrane-Fused Circulating Extracellular Vesicles Protect the Heart from Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion injury (I/RI) may potentiate cardiac remodeling and heart failure, while effective therapies for I/RI remain lacking. Circulating human plasma-derived extracellular vesicles (hEV) have great potential to protect against I/RI. However, the effective delivery of hEV in vivo remains a limiting factor for clinical application. The present study constructs a biomimetic delivery system of platelet membrane-fused hEV (P-hEV), utilizing the natural affinity of platelets for hEV delivery to the injured vascular and myocardial sites. The results show that platelet membrane and hEV membrane fusion can be achieved through repeated extrusion. Compared to non-modified hEV, P-hEV uptake is greatly enhanced in human umbilical vein endothelial cells (HUVECs) stressed by oxygen-glucose deprivation/reperfusion (OGD/R). Functionally, P-hEV inhibits HUVECand neonatal rat cardiomyocyte(NRCM) apoptosis and promotes HUVECsmigration and tube formation under OGD/R stress in vitro. Intravenous delivery of P-hEV more effectively targets and accumulates at injury sites in the heart. Furthermore, P-hEV significantly enhances protection against acute I/RI and attenuates cardiac remodeling at three weeks post-I/RI. In conclusion, the platelet membrane-fused hEV delivery system enhances the target delivery of EV to protect against myocardial I/RI, presenting a novel drug delivery system for ischemic heart diseases.

Nanoplatforms Potentiated Ablation-Immune Synergistic Therapy through Improving Local Control and Suppressing Recurrent Metastasis.

Minimally invasive ablation has been widely applied for treatment of various solid tumors, including hepatocellular carcinoma, renal cell carcinoma, breast carcinomas, etc. In addition to removing the primary tumor lesion, ablative techniques are also capable of improving the anti-tumor immune response by inducing immunogenic tumor cell death and modulating the tumor immune microenvironment, which may be of great benefit to inhibit the recurrent metastasis of residual tumor. However, the short-acting activated anti-tumor immunity of post-ablation will rapidly reverse into an immunosuppressive state, and the recurrent metastasis owing to incomplete ablation is closely associated with a dismal prognosis for the patients. In recent years, numerous nanoplatforms have been developed to improve the local ablative effect through enhancing the targeting delivery and combining it with chemotherapy. Particularly, amplifying the anti-tumor immune stimulus signal, modulating the immunosuppressive microenvironment, and improving the anti-tumor immune response with the versatile nanoplatforms have heralded great application prospects for improving the local control and preventing tumor recurrence and distant metastasis. This review discusses recent advances in nanoplatform-potentiated ablation-immune synergistic tumor therapy, focusing on common ablation techniques including radiofrequency, microwave, laser, and high-intensity focused ultrasound ablation, cryoablation, and magnetic hyperthermia ablation, etc. We discuss the advantages and challenges of the corresponding therapies and propose possible directions for future research, which is expected to provide references for improving the traditional ablation efficacy.

Biologically-Coupled Bisphosphonate Chaperones Effectively Deliver Molecules to the Site of Soft Tissue-Bone Healing.

Tendon injuries are common and often treated surgically, however, current tendon repair healing results in poorly organized fibrotic tissue. While certain growth factors have been reported to improve both the strength and organization of the repaired enthesis, their clinical applicability is severely limited due to a lack of appropriate delivery strategies. In this study, we evaluated a recently developed fluorescent probe, Osteoadsorptive Fluorogenic Sentinel-3 (OFS-3) that is composed of a bone-targeting bisphosphonate moiety linked to fluorochrome and quencher molecules joined via a cathepsin K-sensitive peptide sequence. Using a murine Achilles tendon-to-bone repair model, bisphosphonate-based and/or Ctsk-coupled imaging probes were applied either locally or systemically. Fluorescence imaging was used to quantify the resultant signal in vivo. After tendon-bone repair, animals that received either local or systemic administration of imaging probes demonstrated significantly higher fluorescence signal at the repair site compared to the sham surgery group at all time points (p<0.001), with signal peaking at 7 to 10 days after surgery. Our findings demonstrate the feasibility of using a novel bisphosphonate-based targeting and Ctsk-activated delivery of molecules to the site of tendon-to-bone repair and creates a foundation for further development of this platform as an effective strategy to deliver bioactive molecules to sites of musculoskeletal injury. This article is protected by copyright. All rights reserved.

Microfluidic Formulation of Curcumin-Loaded Multiresponsive Gelatin Nanoparticles for Anticancer Therapy.

Current anticancer research shows that a combination of multiple treatment methods can greatly improve the killing of tumor cells. Using the latest microfluidic swirl mixer technology, combined with chemotherapy and photothermal-ablation therapy, we developed multiresponsive targeted antitumor nanoparticles (NPs) made of folate-functionalized gelatin NPs under 200 nm in size and with encapsulated CuS NPs, Fe3O4 NPs, and curcumin (Cur). By exploring gelatin's structure, adjusting its concentration and pH, and fine-tuning the fluid dynamics in the microfluidic device, the best preparation conditions were obtained for gelatin NPs with an average particle size of 90 ± 7 nm. The comparative targeting of the drug delivery system (DDS) was demonstrated on lung adenocarcinoma A549 cells (low level of folate receptors) and breast adenocarcinoma MCF-7 cells (high level of folate receptors). Folic acid helps achieve targeting and accurate delivery of NPs to the MCF-7 tumor cells. The synergistic photothermal ablation and curcumin's anticancer activity are achieved through infrared light irradiation (980 nm), while Fe3O4 is guided with an external magnetic field to target gelatin NPs and accelerate the uptake of drugs, thus efficiently killing tumor cells. The method described in this work is simple, easy to repeat, and has great potential to be scaled up for industrial production and subsequent clinical use.

Cytotoxic Effect of Caffeic Acid Loaded in Chitosan-Grafted Carbon Nanotubes on MDA-MB-231 Breast Cancer Cell Lines

Breast cancer (BC) is the most common cancer leading to death depending on the stage of cancer. Targeting and drug delivery is an important strategy for cancer therapy such as BC. Destroying cancer cells and minimal damage to normal cells using nanotechnology strategy, especially carbon nanotube (CNT), is a key element in this area. Caffeic acid belongs to the polyphenol compound with anti-tumor activity. In this study, the viability of the MDA-MB-231 cell line was determined after exposing to the caffeic acid (100 µg/ml), oxidant carbon nanotube (OCNT)/caffeic acid (80 µg/ml), and chitosan (CS)/OCNT/caffeic acid (30 µg/ml) at 24 h post-exposure using 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The levels of gene and protein expression of Bax and Bcl-2 were investigated using real-time PCR and Western blotting, respectively. The apoptotic effect of caffeic acid, OCNT/caffeic acid, and CS/OCNT/caffeic acid on MDA-MB-231 was examined by flow cytometry using annexin VI. The data obtained represented that CS/OCNT/caffeic acid, OCNT/caffeic acid, and caffeic acid inhibited cell proliferation. Both mRNA and protein expression levels of Bax and Bcl-2 were up- and down-regulated compared with the control cells. However, the most effect belonged to the CS/OCNT/caffeic acid. The flow cytometry data represented that CS/OCNT/caffeic acid is very effective against MDA-MB-231. Based on the results, the CS/OCNT/caffeic acid showed the highest apoptotic effect on the MDA-MB-231 compared with the OCNT/caffeic acid and caffeic acid. The CS/OCNT/caffeic acid, OCNT/caffeic acid, and caffeic acid have toxicity for MDA-MB-231 cells through an apoptotic pathway by up-regulation of Bax expression level and down-regulation of Bcl-2.

A cascade-responsive nanoplatform with tumor cell-specific drug burst release for chemotherapy.

Most of the nanomedicines can reduce the side effects of anti-tumor chemical drugs but do not have good enough therapeutic efficacy, largely due to the sustained drug release profile. It might be a promising alternative strategy to develop a cascade-responsive nanoplatform against tumor with the burst release of chemotherapeutics based on the highly efficient tumor cell targeting delivery. In this work, we constructed innovative nanoparticles (PMP/WPH-NPs) consisting of two functional polymers. PMP contained the MMP-2 enzyme sensitive linker and disulfide bond, which could respond to the tumor-overexpressing enzyme MMP-2 and high-level glutathione. While WPH promoted tumor penetration and acid-responsive drug release by modifying cellular penetrating peptides and polymerizing L-histidine. PMP/WPH-NPs exhibited outstanding features including longer blood circulation time, promoted tumor-specific accumulation, enhanced tumor penetration and efficient escape from lysosomes. Subsequently, the model drug paclitaxel (PTX), widely used in the tumor chemotherapy, was encapsulated into PMP/WPH-NPs via an emulsion solvent evaporation method. Within a short period of time, PTX-PMP/WPH-NP in simulated tumor cellular microenvironment could release 8 times more PTX than that in the physiological environment, demonstrating a good potential in tumor cell-specific burst drug release. In addition, PTX-PMP/WPH-NPs exhibited stronger anti-tumor activity than PTX in vitro and in vivo, which also had good biocompatibility according to the hemolysis assay and H&E staining. In summary, our work has succeeded in designing an original polymeric nanoplatform for programmed burst drug release based on the tailored tumor targeting delivery system. This new approach would facilitate the clinical translation of more anti-tumor nanomedicines. STATEMENT OF SIGNIFICANCE: Biomaterials responsive to the tumor-specific stimulus has conventionally used in the targeted-delivery of anti-tumor drugs. However, the levels of common stimulus are not uniformly distributed and not high enough to effectively trigger drug release. In an effort to achieve a better specific drug release and promote the chemotherapeutic efficacy, we constructed a cascade responsive nanoplatform with tumor cell-specific drug burst release profile. The tailored biomaterial could overcome the bio-barriers in vivo and succeeded in the programmed burst drug release based on the tumor cell-specific delivery of chemotherapeutics.

Biomimetic nanoplatform with H2O2 homeostasis disruption and oxidative stress amplification for enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) is a powerful cancer treatment strategy by producing excessive amount of reactive oxygen species (ROS) to kill cancer cells. However, the inadequate hydrogen peroxide (H2O2) supply and antioxidant defense systems in tumor tissue significantly impair the therapeutic effect of CDT, hindering its further applications. Herein, we present an intelligent nanoplatform with H2O2 homeostasis disruption and oxidative stress amplification properties for enhanced CDT. This nanoplatform is obtained by encapsulating glucose oxidase (GOx) in a pH- and glutathione (GSH)-responsive degradable copper doped-zeolitic imidazolate framework (Cu-ZIF8), followed by loading of 3-amino-1,2,4-triazole (3AT) and modification of hyaluronic acid (HA) for tumor targeting delivery. The GOx@Cu-ZIF8-3AT@HA not only reduces energy supply and increases H2O2 level by exhausting intratumoral glucose, but also disturbs tumor antioxidant defense systems by inhibiting the activity of catalase (CAT) and depleting intracellular GSH, resulting in disrupted H2O2 homeostasis in tumor. Moreover, the elevated H2O2 will transform into highly toxic hydroxyl radical (·OH) by Cu+ that generated from redox reaction between Cu2+ and GSH, amplifying the oxidative stress to enhance the CDT efficacy. Consequently, GOx@Cu-ZIF8-3AT@HA has significantly inhibited the 4T1 xenograft tumor growth without discernible side effects, which provides a promising strategy for cancer management. STATEMENT OF SIGNIFICANCE: The inadequate H2O2 level and antioxidant defense system in tumor tissues significantly impair the therapeutic effect of CDT. Herein, we developed an intelligent nanoplatform with H2O2 homeostasis disruption and oxidative stress amplification properties for enhanced CDT. In this nanoplatform, GOx could exhaust intratumoral glucose to reduce energy supply accompanied with production of H2O2, while the suppression of CAT activity by 3AT and depletion of GSH by Cu2+ would weaken the antioxidant defense system of tumors. Ultimately, the raised H2O2 level would convert to highly toxic •OH by Fenton-like reaction, amplifying the CDT efficacy. This work provides a promising strategy for cancer management.

TRANSFERSOMES AS NOVEL DRUG DELIVERY SYSTEM

Transdermal drug delivery appears to be most vital drug delivery system because of its merit over conventional systems. Transferosomes &amp; the fundamental concept of transfersomes were launched by Gregor Cevc in the year 1991. The name means carrying body and is derived from the Latin word transferre, meaning to carry across and the Greek word soma, meaning a body. Novel drug delivery system aims to deliver the drug at a rate directed by need of body during the period of treatment and channel the active entity to the site of action. Transferosome is one of the novel vesicular drug delivery system which consists of phospholipids, surfactant and water for enhanced transdermal delivery. Transferosomes are able to reach intact deeper regions of the skin after topical drug administration while delivering higher concentrations of active substances making them a successful carrier for transdermal applications. These vesicular systems can deliver low as well as high molecular weight compounds. Targeted and controlled release formulations can also be prepared by transferosomes as it can accommodate drug molecules with wide range of solubility. Various strategies can be used to augment the transdermal delivery which includes iontophoresis, electrophoresis, sonophoresis, chemical permeation enhancers, microneedles, &amp; vesicular system (liposomes, niosomes, elastic liposomes such as ethosomes &amp; transfersomes). It exists as an ultra-deformable complex having a hydrated core surrounded by a complex layer of lipid. It penetrates the stratum corneum by either intracellular route or the transcellular route by the generation of osmotic gradient. Advantages of Transferosomes are wide range of solubilities, better penetration, biocompatible and biodegradable etc. Disadvantages of Transferosomes are oxidative degradation, expensive, etc. The transfersomes were formulated by the conventional rotary evaporation sonication method. Transferosomes can be applied in controlled release, transportation of large molecular weight compounds, target delivery to peripheral subcutaneous tissues, transdermal immunization etc.

Phage-Ce6-Manganese Dioxide Nanocomposite-Mediated Photodynamic, Photothermal, and Chemodynamic Therapies to Eliminate Biofilms and Improve Wound Healing

Biofilms have become one of the fundamental issues for chronic infections, while traditional therapies are often ineffective in removing quiescent (persister) cells from biofilms, resulting in a variety of implant-related or nosocomial infections. Recently, bacteriophage (phage) therapy has reflourished in research and clinical trials. However, phage therapy alone manifested many intrinsic defects, including poor biofilm penetration, incomplete clearance of quiescent cells, etc. In this study, a phage-Chlorin e6 (Ce6)-manganese dioxide nanocomposite (PCM) was constructed by mild biomineralization. The results demonstrated that PCM contained both the vigorous activities of host bacterial targeting and efficient delivery of Ce6 to penetrate the biofilm. Assisted with NIR irradiation, robust reactive oxygen species (ROS) was triggered within the biofilm. In the weak acidic and GSH-rich infection niche, PCM was degraded into ultra-small nanosheets, endowing PCM with moderate photothermal therapy (PTT) effects and considerable Mn2+ release, thus exerting strong chemodynamic therapy (CDT) effects in situ. In vivo application demonstrated that the combination of PCM application and NIR irradiation strikingly reduced the pathogen loading, activated innate and adaptive immunity, promoted neocollagen rearrangement, and attenuated cicatricial tissue formation. Our research may pave a new way for bacterial treatment, biofilm-related infections, and other diseases caused by bacteria.

Biomimetic Nanoparticle-Mediated Target Delivery of Hypoxia-Responsive Plasmid of Angiotensin-Converting Enzyme 2 to Reverse Hypoxic Pulmonary Hypertension.

Hypoxic pulmonary hypertension (HPH) is characterized by pulmonary vascular sustained constriction and progressive remodeling, which are initiated by hypoxia then with hypoxia-induced additive factors including pulmonary vascular endothelium injury, intrapulmonary angiotension system imbalance, and inflammation. Now HPH is still an intractable disease lacking effective treatments. Gene therapy has a massive potential for HPH but is hindered by a lack of efficient targeted delivery and hypoxia-responsive regulation systems for transgenes. Herein, we constructed the hypoxia-responsive plasmid of angiotensin-converting enzyme 2 (ACE2) with endothelial-specific promoter Tie2 and a hypoxia response element and next prepared its biomimetic nanoparticle delivery system, named ACE2-CS-PRT@PM, by encapsulating the plasmid of ACE2 with protamine and chondroitin sulfate as the core then coated it with a platelet membrane as a shell for targeting the injured pulmonary vascular endothelium. ACE2-CS-PRT@PM has a 194.3 nm diameter with a platelet membrane-coating core-shell structure and a negatively charged surface, and it exhibits higher delivery efficiency targeting to pulmonary vascular endothelium and hypoxia-responsive overexpression of ACE2 in endothelial cells in a hypoxia environment. In vitro, ACE2-CS-PRT@PM significantly inhibited the hypoxia-induced proliferation of pulmonary smooth muscle cells. In vivo, ACE2-CS-PRT@PM potently ameliorated the hemodynamic dysfunction and morphological abnormality and largely reversed HPH via inhibiting the hypoxic proliferation of pulmonary artery smooth muscle cells, reducing pulmonary vascular remodeling, restoring balance to the intrapulmonary angiotension system, and improving the inflammatory microenvironment without any detectable toxicity. Therefore, ACE2-CS-PRT@PM is promising for the targeted gene therapy of HPH.

Nanoemulsion carriers for drug delivery: Assessment of environmental hazards

Nanoemulsions (NEs) have been extensively studied as carriers for drug delivery, since these provide a good alternative to the existing non-nano systems, while promoting their target delivery and controlled release. NEs are considered safe drug carriers from a pre-clinical perspective, but there is currently no information on their ecotoxicological effects. In the present study we investigated the toxicity of a NE material (lecithin, sunflower oil, borate buffer) designed to be used as a liposomal excipient for eye drops, further referred to as (Lipid Particle:LP) LP_Eye and its dispersant (borate buffer) (LP_Eye disp.). Effects were assessed using two model species in soil ecotoxicology in LUFA 2.2 soil: Enchytraeus crypticus (Oligochaeta) and Folsomia candida (Collembola), based on the OECD standard guideline (28 days) and its extension, a longer-term exposure (56 days). The endpoints evaluated included survival, reproduction, and size. LP_Eye and LP_Eye disp. were toxic to E. crypticus and F. candida, affecting all measured endpoints. The toxicity of LP_Eye in E. crypticus seemed to be induced by the dispersant, whereas for F. candida, more sensitive, this was less explanatory. There were no indications that toxicity increased with longer exposure. Current results provide ecotoxicological data for a group of NMs that was absent, revealing toxicity to relevant environmental species. Indications were that the dispersant contributed to most of the observed effects, thus there is room to improve the formulation and achieve lower environmental impact.

Exploration of polydopamine capped bimetallic oxide (CuO-NiO) nanoparticles inspired by mussels for enhanced and targeted paclitaxel delivery for synergistic breast cancer therapy

Integration of antitumor drug and metallic nanoparticles in a polymeric nanosystem with effective properties is an emerging and promising tool to improve tumor treatment. Nevertheless, there is still a clinical need for multifunctional nanoparticles (NPs) to be developed for an “all-in-one” platform with specific targeting, less side effects and high therapeutic efficacy. In this research, pH-responsive bimetallic oxide-multifunctional NPs wrapped by polydopamine polymer for simultaneous cancer cell targeting and drug delivery were synthesized based on simple metal nanoparticle-ligand interactions. We explored a unique nanosystem of mussel inspired, polydopamine complexed with copper/nickel oxide NPs (CuO-NiO@PDA NPs). CuO-NiO@PDA NPs were then loaded with anticancer drug paclitaxel (PTX) via electrostatic or π-π stacking interaction and functionalized with folic acid (FA), a tumor-targeting ligand, to form CuO-NiO@PDA-PTX/FA NPs. Results highlight therapeutic potential of CuO-NiO@PDA/FA NPs as paclitaxel delivery nanocarrier in breast cancer therapy with sustained drug release pattern due to their increased stability, biocompatibility and antitumor efficacy. Cell viability was demonstrated in vitro using AO/EB dual staining, and its anticancer potential was confirmed by a reactive oxygen species (ROS) assay and mitochondrial membrane potential staining experiments. Consequently, our designed CuO-NiO@PDA-PTX/FA NPs appear to be promising multipurpose nanocarriers with therapeutic potential for MCF-7 tumor targeting and penetration.

Aptamer modified Ti3C2 nanosheets application in smart targeted photothermal therapy for cancer

BackgroundTi3C2 is a type of transition metal carbides and nitrides (MXenes) with high light-to-heat conversion efficiency property, which has been widely used in cancer treatment recently. In fact, active targeting delivery of MXenes nanomaterials with targeting molecule could enhance the therapeutic efficacy. However, targeted therapy of MXenes has not been further studied in the past. Aptamers (Apt) with excellent affinity and high specificity properties have been widely used as targeting tools. Predictably, the incorporation of Apt into Ti3C2 nanomaterials will offer an unprecedented opportunity in the research fields of cancer targeted therapy.ResultsTransmembrane glycoprotein mucin 1 (MUC1) is overexpressed on the surface of MCF-7 cells, and MUC1 Apt (Apt-M) could target MCF-7 cells with high affinity and specificity. Here, a smart targeting nanotherapeutic system Ti3C2/Apt-M was fabricated, which could specifically recognize and enter in MCF-7 cells. Benefitting from the desirable targeted performance of Apt-M, MCF-7 cells completed the ingestion process of Ti3C2/Apt-Mf nanosheets within 4 h, and Apt-M facilitated the entry of the Ti3C2/Apt-Mf nanosheets into MCF-7 cells. Besides, Ti3C2/Apt-M nanosheets exhibited the potential as an outstanding photothermal agent (PTA) because of the photothermal performance inherited from wrapped Ti3C2 nanosheets. As demonstrated, upon 808 nm laser irradiation, the Ti3C2/Apt-M nanotherapeutic system displayed a satisfactory antitumor effect by targeted photothermal therapy both in vitro and in vivo.ConclusionThis study provides a new idea for the development of MXenes nanotherapeutic system with high active targeting performance.Graphical

Expression of TFRC helps to improve the antineoplastic effect of Ara-C on AML cells through a targeted delivery carrier

BackgroundCurrently, high doses of cytarabine arabinoside (Ara-C)-based combined chemotherapy are commonly used in acute myeloid leukemia (AML) therapy, but severe adverse effects and poor suppression effects in leukemia cells limit the clinical therapeutic efficiency of Ara-C-based chemotherapy due to a lack of targeting selectivity. To improve the therapeutic effect of Ara-C in AML, here, since we confirmed that transferrin receptor 1 (TFRC) expression in AML cells was constant, we generated Ara-C@HFn by encapsulating free Ara-C into self-assembled heavy ferritin chain (HFn, the ligand of TFRC) nanocages.ResultsThe analysis of clinically relevant data suggested that the high expression levels of TFRC from AML cells would not decrease significantly after treatment with Ara-C. Ara-C@HFn can be efficiently internalized by leukemia cells, showing stronger cytotoxic effects in vitro and reducing the burden of leukemia in AML mice more effectively in vivo than free Ara-C. Ara-C@HFn treatment showed no acute toxicity in visceral organs of mice. Moreover, the analysis of clinically relevant data also suggested that there are several drugs (such as tamibarotene and ABT199) that would not cause significant expression down-regulation of TFRC in AML cells (after treatment).ConclusionThe above results suggested that TFRC can be used as a constant and effective target for drug targeting delivery of AML cells. Thus Ara-C@HFn treatment can become a safe and efficient strategy for AML therapy by specifically delivering Ara-C to AML cells. Besides, the HFn nanocages are promising for improving antineoplastic effect of other AML-related therapy drugs that do not cause downregulated expression of TFRC in AML cells.Graphical

Construction of cyclodextrin microporous organic network based drug delivery platform for controllable release and targeting delivery of doxorubicin

Rational design and fabrication of effective drug delivery systems (DDS) are crucial for improving the therapeutic effectiveness and overcoming the shortcomings of chemotherapy. Herein, we report the construction of a novel cyclodextrin microporous organic network (CD-MON)-based DDS via a convenient thiol‑yne click reaction and dehydration condensation modification for the controllable release and targeted delivery of doxorubicin (DOX), a typical chemotherapy drug. The constructed DDS afforded multiple hydrophobic, hydrogen-bonding, and host-guest interaction sites, allowing for the efficient loading of DOX. The obtained DDS also exhibited good sustained and long-term release of DOX. Additionally, the proposed DDS offers good biocompatibility and exhibits an obvious aggregation-induced emission. Furthermore, the introduction of folic acid (FA) into the CD-MON-based DDS provided excellent targeting capacity for FA receptor-positive NCI-H226 cells. This study proved the universality of the design, synthesis, and application of CD-MON-based DDS, revealing the great potential of CD-MONs in drug delivery.