High Drug Loading Efficiency Research Articles

A facile method for anti-cancer drug encapsulation into polymersomes with a core-satellite structure

Polymersomes possess the self-assembly vesicular structure similar to liposomes. Although a variety of comparisons between polymersomes and liposomes in the aspects of physical properties, preparation and applications have been elaborated in many studies, few focus on their differences in drug encapsulation, delivery and release in vitro and in vivo. In the present work, we have provided a modified direct hydration method to encapsulate anti-cancer drug paclitaxel (PTX) into PEG-b-PCL constituted polymersomes (PTX@PS). In addition to advantages including narrow particle size distribution, high colloid stability and moderate drug-loading efficiency, we find that the loaded drug aggregate in small clusters and reside through the polymersome membrane, representing a unique core-satellite structure which might facilitate the sustained drug release. Compared with commercial liposomal PTX formulation (Lipusu®), PTX@PS exhibited superb tumor cell killing ability underlain by multiple pro-apoptotic mechanisms. Moreover, endocytic process of PTX@PS significantly inhibits drug transporter P-gp expression which could be largely activated by free drug diffusion. In glioma mice models, it has also confirmed that PTX@PS remarkably eradicate tumors, which renders polymersomes as a promising alternative to liposomes as drug carriers in clinic.

NIR/pH-responsive chitosan hydrogels containing Ti3C2/AuNRs with NIR-triggered photothermal effect

Remotely multi-responsive chitosan (CS) hydrogels holds great promise in the design of anticancer drug carriers. In this paper, near-infrared (NIR)-/pH-dual responsive CS/β-GP/Ti3C2@AuNRs hybrid hydrogel was prepared based on CS/β-glycerol phosphate disodium salt (β-GP) crosslinking system embedded with NIR-responsive Ti3C2@gold nanorods (AuNRs) nanosheets. Excess β-GP promoted the formation of massive electronegative cavities, which endowed hybrid hydrogels with high drug loading efficiency for electropositive DOX (around 88.5 %). The collapse of chitosan network in acidic medium gave the hybrid hydrogel with distinct pH response. In addition, the distinct temperature increase owing to the strong NIR responsiveness of Ti3C2@AuNRs nanosheets would accelerate the DOX release dramatically. Therefore, NIR-, pH- and thermal-multi-responsiveness would synergistically endow CS/β-GP/Ti3C2@AuNRs hybrid hydrogel with notable NIR-triggered photothermal effect and remotely controllable drug delivery properties.

A mutually beneficial macrophages-mediated delivery system realizing photo/immune therapy.

The accumulation of nanomedicines in tumor tissues determines their therapeutic efficacy. We herein exploit the tropism of macrophages to improve the accumulation and retention time of nanomedicine at tumors. Interestingly, macrophages are not merely as transporters, but killers activated by nanomedicine. The system(M@C-HA/ICG) was established by decorating macrophages with hyaluronic acid-modified hollow mesoporous carbon (C) nanoparticles loading indocyanine green (ICG). Notably, C nanoparticles with superior photothermal conversion capability not merely guarantee the efficient delivery of ICG through high drug loading efficiency and inhibiting the premature leaky, but effectually activate the polarization of macrophages. The results exhibited that those activated macrophages could release pro-inflammatory cytokines (NO, TNF-α, IL-12), while M@C-HA/ICG afforded about 2-fold higher tumor accumulation compared with pure nanoparticle C-HA/ICG and produced heat and singlet oxygen (1O2) under irradiation of an 808nm laser, realizing the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and cytokines-mediated immunotherapy. Specially, we also investigated the relationship of singlet oxygen (1O2) or temperature and tumor-killing activity for understanding the specific effectual procedure of PDT/PTT synergistic therapy. Overall, we firstly established an "all active" delivery system integrating the features of nanomedicine with biological functions of macrophages, providing a novel insight for cell-mediated delivery platform and tumor targeted multimodality anti-cancer therapy.

Nanocrystals: An Approachable Delivery System for Anticancer Therapeutics.

Cancer accounts for the high mortality rate and limits the life expectancy of an individual. As per the WHO report of 2020, cancer accounts for >10 million deaths globally. Scientists are continuously pitching toward the development of novel techniques to combat this menace and enhance the efficacy of prevailing molecules. In the early phases of the drug development process, >40% of promising new therapeutic molecules are hydrophobic. Low aqueous solubility results in compromised bioavailability on administration. This limitation is a major drawback for the therapeutic use of anticancer drugs. Drug nanocrystals (NCs) have sparked a lot of interest in drug delivery. This might be due to their excellent physicochemical characteristics like tailored dissolution, high drug loading efficiency, extended circulation period, and high structural stability. There are 'n' a number of the characteristics that make drug nanocrystals a promising formulation for the treatment of cancer. In the last few years, many hydrophobic or lipophilic drugs like camptothecin, paclitaxel, cyclosporin, busulfan, and thymectacin have been formulated as drug nanocrystals against anticancer therapeutics. Various formulation technologies have been developed in conjunction with nanocrystal development. This includes top-down approaches, bottom-up approaches, as well as combination technology. In this article, we will focus on the various manufacturing processes, biological fate and therapeutic applications of NCs, and future perspectives in the management of cancer.

Amentoflavone-loaded nanoparticles enhanced chemotherapy efficacy by inhibition of AKR1B10

Therapeutic nanoparticles can be combined with different anticancer drugs to achieve a synergistic therapy and avoid the limitations of traditional medicine and thus have clinical prospects for cancer. Herein, an effective nanoplatform was developed for self-assembling AMF@DOX-Fe3+-PEG nanoparticles (ADPF NPs) via the coordination of ferric ions (Fe3+), amentoflavone (AMF), doxorubicin (DOX), and PEG-polyphenol. The ADPF NPs possessed high drug loading efficiency, good stability and dispersion in water, prolonged blood circulation, and pH-dependent release, which leading to targeted drug transport and enhanced drug accumulation in the tumor. The AMF from the ADPF NPs could inhibit the expression of the Aldo-keto reductase family 1B10 (AKR1B10) and nuclear factor-kappa B p65 (NF-κB p65), which reduced the cardiotoxicity induced by DOX and enhanced the chemotherapy efficacy. This study established a new strategy of combining drug therapy with a nanoplatform. This new strategy has a wide application prospect in clinical tumor therapy.

PLGA-Based Nanoplatforms in Drug Delivery for Inhibition and Destruction of Microbial Biofilm.

The biofilm community of microorganisms has been identified as the dominant mode of microbial growth in nature and a common characteristic of different microorganisms such as Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. The biofilm structure helps in the protection from environmental threats including host immune system and antimicrobial agents. Thus, the biofilm community has led to a higher prevalence of multidrug-resistant (MDR) strains in recent years. In this regard, the use of a new class of antibiotics, natural compounds, and anti-biofilm enzymes has been considered for the destruction of the microbial biofilm. However, different drawbacks such as low penetration, high susceptibility to degradation, instability, and poor solubility in aqueous solutions limit the use of anti-biofilm agents (ABAs) in a clinical setting. As such, recent studies have been using poly lactic-co-glycolic acid (PLGA)-based nanoplatforms (PLGA NPFs) for delivery of ABAs that have reported promising results. These particles, due to proper drug loading and release kinetics, could suppress microbial attachment, colonization, and biofilm formation for a long time. Additionally, PLGA NPFs, because of the high drug-loading efficiencies, hydrophilic surface, negative charge, and electrostatic interaction, lead to effective penetration of antibiotics to the deeper layer of the biofilm, thereby eliminating the microbial biofilm. Thus, PLGA NPFs could be considered as a potential candidate for coating catheters and other medical material surfaces for inhibition and destruction of the microbial biofilm. However, the exact interaction of PLGA NPFs and the microbial biofilm should be evaluated in animal studies. Additionally, a future goal will be to develop PLGA formulations as systems that can be used for the treatment of the MDR microbial biofilm, since the exact interactions of PLGA NPFs and these biofilm structures are not elucidated. In the present review article, we have discussed various aspects of PLGA usage for inhibition and destruction of the microbial biofilm along with different methods and procedures that have been used for improving PLGA NPF efficacy against the microbial biofilm.

Size Changeable Nanomedicines Assembled by Noncovalent Interactions of Responsive Small Molecules for Enhancing Tumor Therapy.

The size of nanocarriers strongly affects their performance in biological systems, especially the capacity to overcome various barriers before delivering the payloads to destinations. However, the optimum size varies at different delivery stages in cancer therapy due to the complicated tumor microenvironment. Relatively large particles are favored for long-term circulation in vivo, while smaller particles contribute to deep penetration into tumor tissues. This dilemma in the size of particles stimulates the development of stimuli-responsive size-shrinking nanocarriers. Herein, we report a facile strategy to construct a tumor-triggered tannic acid (TA) nanoassembly with improved drug delivery efficiency. Cystamine (CA), a small molecule with a disulfide bond, is thus used to mediate TA assembling via cooperative noncovalent interactions, which endows the nanoassembly with intrinsic pH/GSH dual-responsiveness. The obtained TA nanoassemblies were systematically investigated. DOX encapsulated nanoassembly labeled TCFD NP shows high drug loading efficiency, pH/GSH-responsiveness and significant size shrinkage from 122 to 10 nm with simultaneous drug release. The in vitro and in vivo experimental results demonstrate the excellent biocompatibility, sufficient intracellular delivery, enhanced tumor retention/penetration, and superior anticancer efficacy of the small-molecule-mediated nanoassembly. This noncovalent strategy provides a simple method to fabricate a tumor-triggered size-changeable delivery platform to overcome biological barriers.

ZIF-8 nanoparticles coated with macrophage-derived microvesicles for sustained, targeted delivery of dexamethasone to arthritic joints

Dexamethasone sodium phosphate (Dex) is widely used in the clinic for the treatment of rheumatoid arthritis. However, it circulates in the blood for a short time and it is linked to a high risk of severe side effects caused by repeated dosing. Here, we encapsulated Dex onto zeolitic imidazolate framework-8 (ZIF-8) to prepare metal–organic framework nanoparticles with high drug loading efficiency. To prevent clearance by the mononuclear phagocyte system and extend time in circulation, the nanoparticles were also camouflaged with macrophage-derived microvesicles (MV) to obtain the biomimetic drug delivery system MV/Dex/ZIF-8. In vitro and in vivo experiments showed that the nanosystem had high drug loading and encapsulation efficiency, high stability, and long circulation time, and it permitted sustained drug release longer in inflamed joint tissues. Our study provides new insights into designing camouflaged drug carriers to prevent their phagocytosis and prolong their time in circulation.

Redox-responsive carrier based on fluorinated gemini amphiphilic polymer for combinational cancer therapy

Polymeric micelle has emerged as an efficient implement to overcome the shortcomings of conventional cancer chemotherapy due to its superior solubility of hydrophobic drugs and less side effects of drugs. However, insufficient dilution resistance and ordinary therapeutic effect severely restrict the further translation of current drug-loaded polymeric micelles. Here, we showed that well-defined G-Fn (n = 5, 9, 13) polymeric micelles possessed excellent capabilities as a drug carrier in light of high drug loading content, high stability and precise drug release combined with wonderful endocytosis efficiency to tumors. The representative G-F13 exhibited an excellent dilution resistance, outstanding high drug loading content (22 wt%) and drug loading efficiency (82%), which might be attributed to the extremely low critical micelle concentration conferred by its special Gemini structure and the superhydrophobicity of the fluorocarbon chain. Furthermore, the “cross-linked” internal fluoride membrane consisted of the two chains of the Gemini structure made G-F13 stable even after 24 h of incubation in 10% fetal bovine serum (FBS). The camptothecin (CPT) release was selectively triggered by glutathione (GSH) and H2O2, reaching 75% and 85% after 24 h respectively, in which only 15% of drugs leak under physiological conditions. The CCK-8 assays of Hela cells showed that CPT-loaded G-F13 micelles had high cell compatibility (200 μg/mL, 93% cell viability, 48 h) and high cancer cytotoxicity (IC50 0.1 μg/mL). Notably, a tenfold lower dosage of loaded CPT had an higher tumor growth inhibition than the free CPT. This result was attributed to the combined treatment of fluorinated drug carriers were more likely to penetrate the cell membrane to enter tumor cells, the cytotoxicity of selenic acid generated after the oxidation of G-F13 and the large amounts of CPT after redox release. Excellent physical and chemical properties as well as good therapeutic effects reveal that G-F13 can act as a promising drug carrier to widely use in cancer chemotherapy.

Hollow chain-like SiO2/ZnO nanocomposites: Electrospinning synthesis, defect-related luminescence, and applications for drug delivery

A variety of mesoporous SiO2/ZnO hollow nanochains with different molar ratios of Zn/Si have been synthesized by electrospinning followed by a subsequent calcination process. The hollow nanochains consist of long nanotubes that are strung together with nanobeads, and exhibit a typical mesoporous structure, large specific surface area, and high biocompatibility. The SiO2/ZnO nanocomposites show intense defect-related luminescence with blue emission under ultraviolet excitation, which make them possible to monitor and track the drug release process and the fate of the material when used as an inorganic drug carrier. The drug loading reveals that the SiO2/ZnO nanocomposites shows high drug loading efficiency and the release pattern displays a sustained release process after the initial burst. In particular, the SiO2/ZnO hollow nanochains are stable in normal physiological environment and can collapse and decompose in acid buffer solution, which can simultaneously accelerate the drug release process and achieve the pH-responsive drug release pattern. The as-synthesized nanocomposites may act as a promising drug carrier for tumor-targeted therapy due to their well-defined morphology, good biocompatibility, high drug loading capacity, pH-responsive release pattern, eminent biodegradability, and potent anti-cancer effect.

Fluorescence-Reporting-Guided Tumor Acidic Environment-Activated Triple Photodynamic, Chemodynamic, and Chemotherapeutic Reactions for Efficient Hepatocellular Carcinoma Cell Ablation.

Tumor acidic environment-activated combination therapy holds great promise to significantly decrease side effects, circumvent multiple drug resistance, and improve therapeutic outcomes for cancer treatment. Herein, Sorafenib/ZnPc(PS)4@FeIII-TA nanoparticles (SPFT) are designed with acid-environment turned-on fluorescence to report the activation of triple therapy including photodynamic, chemodynamic, and chemotherapy on hepatocellular carcinoma. The SPFT are composed of SP cores formulated via self-assembly of sorafenib and ZnPc(PS)4, with high drug loading efficiency, and FeIII-TA shells containing FeCl3 and tannic acid. Importantly, the nanoparticles suppress reactive oxygen species (ROS) generation of ZnPc(PS)4 due to their formation in nanoparticles, while assisting simultaneous uptake of the uploaded drugs in cancer cells. The tumor acidic environment initiates FeIII-TA decomposition and accelerates a chemodynamic reaction between FeII and H2O2 to generate toxic •OH. Then, the SP core is decomposed to separate ZnPc(PS)4 and sorafenib, which leads to fluorescence turning-on of ZnPc(PS)4, expedited photodynamic reactions, and burst release of sorafenib. Notably, SPFT shows low dark cytotoxicity to normal cells but exerts high potency on hepatocellular carcinoma cells under near-infrared light irradiation, which is much more potent than either sorafenib or ZnPc(PS)4 alone. This research offers a facile nanomedicine design strategy for cancer therapy.

PH/Redox/Lysozyme-Sensitive Hybrid Nanocarriers With Transformable Size for Multistage Drug Delivery.

The majority of current nanocarriers in cancer treatment fail to deliver encapsulated cargos to their final targets at therapeutic levels, which decreases the ultimate efficacy. In this work, a novel core–shell nanocarrier with a biodegradable property was synthesized for efficient drug release and subcellular organelle delivery. Initially, silver nanoparticles (AgNPs) were grafted with terminal double bonds originating from N, N′-bisacrylamide cystamine (BAC). Then, the outer coatings consisting of chitosan (CTS) and polyvinyl alcohol (PVA) were deposited on the surface of modified AgNPs using an emulsion method. To improve the stability, disulfide-containing BAC was simultaneously reintroduced to cross-link CTS. The as-prepared nanoparticles (CAB) possessed the desired colloidal stability and exhibited a high drug loading efficiency of cationic anticancer agent doxorubicin (DOX). Furthermore, CAB was tailored to transform their size into ultrasmall nanovehicles responding to weak acidity, high glutathione (GSH) levels, and overexpressed enzymes. The process of transformation was accompanied by sufficient DOX release from CAB. Due to the triple sensitivity, CAB enabled DOX to accumulate in the nucleus, leading to a great effect against malignant cells. In vivo assays demonstrated CAB loading DOX held excellent biosafety and superior antitumor capacity. Incorporating all the benefits, this proposed nanoplatform may provide valuable strategies for efficient drug delivery.

Bioengineered Platelets Combining Chemotherapy and Immunotherapy for Postsurgical Melanoma Treatment: Internal Core-Loaded Doxorubicin and External Surface-Anchored Anti-PD-L1 Antibody Backpacks.

The pivotal factors affecting the survival rate of patients include metastasis and tumor recurrence after the resection of the primary tumor. Anti-PD-L1 antibody (aPD-L1) has promising efficacy but with some side effects for the off-target binding between aPD-L1 and normal tissues. Here, inspired by the excellent targeting capability of platelets with respect to tumor cells, we propose bioengineered platelets (PDNGs) with inner-loaded doxorubicin (DOX) and outer-anchored aPD-L1-cross-linked nanogels to reduce tumor relapse and metastatic spread postoperation. The cargo does not impair the normal physiological functions of platelets. Free aPD-L1 is cross-linked to form nanogels with a higher drug-loading efficiency and is sustainably released to trigger the T-cell-mediated destruction of tumor cells, reversing the tumor immunosuppressive microenvironment. PDNGs can reduce the postoperative tumor recurrence and metastasis rate, prolonging the survival time of mice. Our findings indicate that bioengineered platelets are promising in postsurgical cancer treatment by the tumor-capturing and in situ microvesicle-secreting capabilities of platelets.

Synthesis of enzyme-responsive theranostic amphiphilic conjugated bottlebrush copolymers for enhanced anticancer drug delivery

Synthesis of polyfluorene (PF) based theranostic amphiphilic copolymers with simultaneously high drug loading efficiency and tumor microenvironment-specific responsiveness for promoted intracellular drug release and enhanced cancer therapy has been rarely reported likely due to the lack of efficient synthetic approaches to integrate these desirable properties. In this work, we recorded the successful preparation of well-defined theranostic amphiliphilic bottlebrush copolymers composing of fluorescent backbone of PF and tunable enzyme-degradable side chains of polytyrosine (PTyr) and POEGMA by integrating Suzuki coupling, NCA ROP and ATRP techniques. Notably, the resulting copolymer, PF25-g-(PTyr26-b-(POEGMA28)2 (P4) with two branched POEGMA brushes tethered to one PTyr termini for each unit could form steady unimolecular micelles with higher fluorescence quantum yield of 18.3% in aqueous and greater entrapment efficiency (EE) of 91.0% for DOX ascribed to the efficient π–π stacking interactions between PTyr blocks and drug molecules and the unique structure of branched hydrophilic brushes with a moderate chain length. DOX@P4 micelles revealed visualization of intracellular trafficking and accelerated drug release due to the enzyme-triggered degradation of PTyr blocks with proteinase K and subsequent deshielding of POEGMA corona for micelle destruction. In vitro and In vivo animal study further verified the intensive therapeutic efficiency with attenuated systematic toxicity. Taken together, we provided a universal strategy toward multifunctional polymeric delivery vehicles based on conjugated PF and biocompatible and degradable polypeptide by integratied Suzuki coupling and NCA ROP, and identified the branched structure of hydrophilic brushes for better performance of bottlebrush copolymers-based micelles for drug delivery applications. Statement of significanceSynthesis of polyfluorene (PF)-based theranostic amphiphilic copolymers with simultaneously high drug loading efficiency and tumor microenvironment-specific responsiveness for promoted intracellular drug release and enhanced cancer therapy has been rarely reported likely due to the lack of efficient synthetic approaches to integrate these desirable properties. We reported herein successful preparation of enzyme-responsive theranostic amphiliphilic bottlebrush copolymers with simultaneously high drug loading efficiency and tumor microenvironment-specific responsiveness for enhanced chemotherapy in vivo. This study therefore not only developed a universal strategy for the construction of multifunction polymeric vehicles based on the conjugated polymer of PF and degradable polypeptide by integrated Suzuki coupling and NCA ROP, but also emphasized the better stability of micelles endowed by the branched hydrophilic brushes than linear ones.

Biocompatible propylene glycol alginate-g-polytetrahydrofuran amphiphilic graft copolymers for highly effective drug carriers

The acylated propylene glycol alginate-g-polytetrahydrofuran amphiphilic graft copolymers (APGA-g-PTHF) with various grafting numbers (GN) of 3–23 per 1000 monosaccharide rings and PTHF (PTMG or PTMO) branches with different molecular weights (Mn,PTHF) of 600–3400 g/mol could be successfully synthesized via nucleophilic substitution of PTHF living chains carrying oxonium ions with the –OH side groups of APGA backbone. The nanophase separation, the hydrophobicity and the surface roughness were increased due to the less restricted movement of hydrophobic PTHF branches to the surface. APGA-g-PTHF graft copolymers behave low cytotoxicity and good anti-protein performance. Interestingly, APGA-g-PTHF amphiphilic graft copolymers could form homogeneous nanospheres (<250 nm) via self-assembly in H2O/CH2Cl2 medium which could be used for drug (ibuprofen or curcumin) carriers having high drug loading efficiency (∼45%) and fast release behavior. The nanospheres carried curcumin behave very higher (10-fold) anticancer effect against HeLa cells than that of curcumin and thus reduce the harmful drug dosage. Moreover, the nanospheres carried drug might enter into HeLa cells and present pH-sensitive drug release. To the best of our knowledge, this is the first example of PGA-based graft copolymers for highly effective nano-carriers and anti-protein surfaces, which would have a prospect in biomedical areas.

Glycosylated Ang-(1-7) MasR Agonist Peptide Poly Lactic-co-Glycolic Acid (PLGA) Nanoparticles and Microparticles in Cognitive Impairment: Design, Particle Preparation, Physicochemical Characterization, and In Vitro Release.

Heart failure (HF) causes decreased brain perfusion in older adults, and increased brain and systemic inflammation increases the risk of cognitive impairment and Alzheimer’s disease (AD). Glycosylated Ang-(1-7) MasR agonists (PNA5) has shown improved bioavailability, stability, and brain penetration compared to Ang-(1-7) native peptide. Despite promising results and numerous potential applications, clinical applications of PNA5 glycopeptide are limited by its short half-life, and frequent injections are required to ensure adequate treatment for cognitive impairment. Therefore, sustained-release injectable formulations of PNA5 glycopeptide are needed to improve its bioavailability, protect the peptide from degradation, and provide sustained drug release over a prolonged time to reduce injection administration frequency. Two types of poly(D,L-lactic-co-glycolic acid) (PLGA) were used in the synthesis to produce nanoparticles (≈0.769–0.35 µm) and microparticles (≈3.7–2.4 µm) loaded with PNA5 (ester and acid-end capped). Comprehensive physicochemical characterization including scanning electron microscopy, thermal analysis, molecular fingerprinting spectroscopy, particle sizing, drug loading, encapsulation efficiency, and in vitro drug release were conducted. The data shows that despite the differences in the size of the particles, sustained release of PNA5 was successfully achieved using PLGA R503H polymer with high drug loading (% DL) and high encapsulation efficiency (% EE) of >8% and >40%, respectively. While using the ester-end PLGA, NPs showed poor sustained release as after 72 h, nearly 100% of the peptide was released. Also, lower % EE and % DL values were observed (10.8 and 3.4, respectively). This is the first systematic and comprehensive study to report on the successful design, particle synthesis, physicochemical characterization, and in vitro glycopeptide drug release of PNA5 in PLGA nanoparticles and microparticles.

The development of a redox-sensitive curcumin conjugated chitosan oligosaccharide nanocarrier for the efficient delivery of docetaxel to glioma cells.

BackgroundA redox-sensitive nanoscale delivery system was developed, based on the hydrophilic chitosan oligosaccharide-ss-hydrophobic curcumin conjugate (CSO-ss-CUR) loaded with docetaxel (DTX), for the targeting and synergistic treatment of gliomas.MethodsRedox-sensitive nanoparticles were loaded with DTX (DTX/CSO-ss-CUR) using the improved ultrasonic-dialysis approach. The morphology and particle size of the loaded nanoparticles were examined by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. The cytotoxicity and cellular uptake of the nanoparticles were assessed in vitro using the C6 glial cell line. The in vivo antitumor efficacy and in vivo biodistribution studies were evaluated using the C6 tumor-bearing Balb/c female mouse model.ResultsThe DTX/CSO-ss-CUR nanoparticles were generally spherical in shape and exhibited desirable particle size (under 250 nm) with high drug loading efficiency (DL) (8.96%±0.56%) and encapsulation efficiency (EE) (35.23%±3.26%). In vitro, the drug was released from the nanoparticles in a redox-sensitive manner. The DTX/CSO-ss-CUR nanoparticles exhibited superior hemocompatibility in the hemolytic test and in vitro cytotoxicity and live/dead cell staining experiments revealed a higher cytotoxicity to glioma cells compared to the free drug. Furthermore, in vitro uptake experiments using C6 glioma cells demonstrated that the CSO-ss-CUR nanoparticles had good cell penetration ability. The in vivo antitumor efficacy and in vivo biodistribution studies suggested that the CSO-ss-CUR nanoparticles could effectively inhibit C6 tumor growth. More importantly, after intravenous injection, more CSO-ss-CUR nanoparticles were concentrated in the brain of the mice than free 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) group.ConclusionsA unique drug delivery system formed by the self-assembly of CSO-ss-CUR was developed and shown to effectively cross the blood-brain barrier (BBB), enriching the abundance of the drug in the brain tissues. This may represent a potential therapeutic strategy for the treatment of gliomas.KeywordsChitosan oligosaccharide (CSO); curcumin (CUR); docetaxel (DTX); glioma

Fabrication of pH responsive FU@Eu-MOF nanoscale metal organic frameworks for lung cancer therapy

Fabrication of biocompatible drug delivery systems (DDS) with enhanced permeation -retention effect and precise targeting is a major challenge in cancer therapy. The present study focused on fabrication of europium metal-organic framework (EuMOF) as pH responsive drug delivery system for sea weed polysaccharide fucoidan (FU@Eu-MOF) by one-pot synthesis method and assess its anticancer potential against lung cancer. Fabricated Eu-MOF exhibited high drug loading efficiency (22.15% by wt) and pH responsive controlled release of drug fucoidan (85.3 ± 0.02% in 48 h at pH 5.0). Material characterization revealed the formation of monodispersed uniform rod shaped structure decorated with fucoidan on the surface with average particle size of 71 ± 0.21 nm. Results of anticancer studies revealed that FU@Eu-MOF showed enhanced anticancer potential (IC50 value 32.17 ± 0.06 μg/ml) in lung cancer cells (A549) when compared to fucoidan alone (IC50 60.34 ± 0.03 μg/ml). Mechanism of anticancer potential revealed that FU@Eu-MOF enhanced ROS level inducing mitochondrial dysfunction and DNA damage leading to apoptosis. Safety evaluation studies revealed that FU@Eu-MOF showed neither cytotoxic, nor hemolytic activity under in vitro condition. To conclude the results of the study reveals FU@Eu-MOF as promising biocompatible material for drug delivery system for lung cancer therapy and other biomedical applications.

Cooperative coordination-mediated multi-component self-assembly of “all-in-one” nanospike theranostic nano-platform for MRI-guided synergistic therapy against breast cancer

Carrier-free multi-component self-assembled nano-systems have attracted widespread attention owing to their easy preparation, high drug-loading efficiency, and excellent therapeutic efficacy. Herein, MnAs-ICG nanospike was generated by self-assembly of indocyanine green (ICG), manganese ions (Mn2+), and arsenate (AsO43−) based on electrostatic and coordination interactions, effectively integrating the bimodal imaging ability of magnetic resonance imaging (MRI) and fluorescence (FL) imaging-guided synergistic therapy of photothermal/chemo/chemodynamic therapy within an “all-in-one” theranostic nano-platform. The as-prepared MnAs-ICG nanospike had a uniform size, well-defined nanospike morphology, and impressive loading capacities. The MnAs-ICG nanospike exhibited sensitive responsiveness to the acidic tumor microenvironment with morphological transformation and dimensional variability, enabling deep penetration into tumor tissue and on-demand release of functional therapeutic components. In vitro and in vivo results revealed that MnAs-ICG nanospike showed synergistic tumor-killing effect, prolonged blood circulation and increased tumor accumulation compared to their individual components, effectively resulting in synergistic therapy of photothermal/chemo/chemodynamic therapy with excellent anti-tumor effect. Taken together, this new strategy might hold great promise for rationally engineering multifunctional theranostic nano-platforms for breast cancer treatment.

Highly porous and injectable hydrogels derived from cartilage acellularized matrix exhibit reduction and NIR light dual-responsive drug release properties for application in antitumor therapy

In this work, we developed novel stimuli-responsive injectable hydrogels composed of a highly biocompatible cartilage acellularized matrix (CAM) and a water-soluble cross-linker containing a diselenide bridge by using ultrafast norbornene (Nb)-tetrazine (Tz) click chemistry. The cross-linking reaction between the Nb groups of the CAM and Tz groups of the cross-linker evolved nitrogen gas and resulted in injectable hydrogels with highly porous structures. The synthesized hydrogels demonstrated high drug loading efficiencies (up to 93%), good swelling ratios, and useful mechanical properties. The doxorubicin (DOX)-loaded hydrogels released minimal amounts of DOX in the simulated physiological medium; however, sustained release of DOX was detected under reducing conditions, revealing more than 90% DOX release after 96 h. Interestingly, the indocyanine green (ICG)-incorporated hydrogels produced reactive oxygen species upon exposure to NIR light and exhibited burst release (>50% DOX release) of DOX during the first 4 h, followed by a sustained release phase. In vitro cytocompatibility tests showed that the synthesized CAM-Nb and hydrogels are essentially nontoxic to HFF-1 fibroblast cells and human colorectal adenocarcinoma cells (HT-29), indicating their excellent bioorthogonality and biocompatibility. Furthermore, DOX-loaded and DOX + ICG-loaded hydrogels inhibited the metabolic activities of HT-29 cells after GSH or NIR exposure and induced antitumor effects similar to those of free DOX. Therefore, these biocompatible and reduction-responsive injectable hydrogels, which exhibited on-demand drug release after NIR exposure, could be promising candidates for minimally invasive local delivery of cancer therapeutics.