Targeted Delivery Systems Research Articles

Multifunctional Nano-Biomaterials for Cancer Therapy via Inducing Enhanced Immunogenic Cell Death.

Immunotherapy is considered to be one of the most promising methods to overcome cancer. Immunogenic cell death (ICD), as a special form of cell death that can trigger an antitumor immune response, has attracted increasing attention for cancer immunotherapy. Presently, ICD-mediating immunotherapy needs to overcome many hurdles including a lack of targeted delivery systems for ICD inducers, insufficient antitumor immunity, and the immunosuppressive tumor microenvironment. Recent research has demonstrated that nano-biomaterials exhibit unique biochemphysical properties at the nanoscale, providing a prospective approach to overcoming these obstacles. In this review, the authors first survey the occurrence, processes, and detection methods of ICD. Subsequently, the recent advances of nano-biomaterials applied to enhance ICD according to the key steps in the process of ICD, particularly with a focus on the mechanisms and lifting schemes are investigated. Finally, based on the achievement in the representative studies, the prospects and challenges of nanotechnology in ICD for cancer therapy are discussed to enable clinical translation.

Cancer-Specific Delivery of Proteolysis-Targeting Chimeras (PROTACs) and Their Application to Cancer Immunotherapy.

Proteolysis-targeting chimeras (PROTACs) are rapidly emerging as a potential therapeutic strategy for cancer therapy by inducing the degradation of tumor-overexpressing oncogenic proteins. They can specifically catalyze the degradation of target oncogenic proteins by recruiting E3 ligases and utilizing the ubiquitin-proteasome pathway. Since their mode of action is universal, irreversible, recyclable, long-lasting, and applicable to 'undruggable' proteins, PROTACs are gradually replacing the role of conventional small molecular inhibitors. Moreover, their application areas are being expanded to cancer immunotherapy as various types of oncogenic proteins that are involved in immunosuppressive tumor microenvironments. However, poor water solubility and low cell permeability considerably restrict the pharmacokinetic (PK) property, which necessitates the use of appropriate delivery systems for cancer immunotherapy. In this review, the general characteristics, developmental status, and PK of PROTACs are first briefly covered. Next, recent studies on the application of various types of passive or active targeting delivery systems for PROTACs are introduced, and their effects on the PK and tumor-targeting ability of PROTACs are described. Finally, recent drug delivery systems of PROTACs for cancer immunotherapy are summarized. The adoption of an adequate delivery system for PROTAC is expected to accelerate the clinical translation of PROTACs, as well as improve its efficacy for cancer therapy.

A pH-sensitive hydrogel based on carboxymethylated konjac glucomannan crosslinked by sodium trimetaphosphate: Synthesis, characterization, swelling behavior and controlled drug release

The pH-sensitive hydrogel consisting of carboxymethylated konjac glucomannan (CMKGM) and sodium trimetaphosphate (STMP) was prepared for a potential intestinal targeted delivery system. Both the CMKGM and the CMKGM hydrogel were characterized by FT-IR spectra, X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The Congo red and atomic force microscope (AFM) results showed a coil-to-helix transition of CMKGM in alkaline conditions with the degree of substitution (DS) increased from 0.20 to 0.49. Rheological measurements indicated that the DS and the STMP content collectively influence the mechanical stiffness and swelling properties of the obtained hydrogels. In addition, the swelling behavior of the hydrogels revealed that they were sensitive to pH value changes and were following a Korsmeyer-Peppas gastrointestinal release behavior, indicating that the release was controlled by non-Fickian diffusion. Furthermore, all the results suggested that the prepared pH-sensitive hydrogel may serve as a potential biomaterial for the intestine-targeted delivery system.

Overcoming the On-Target Toxicity in Antibody-Mediated Therapies via an Indirect Active Targeting Strategy.

Antibody-based therapies could be led astray when target receptors are expressed on nontarget sites, and the on-target toxicity poses critical challenges to clinical applications. Here, a biomimetic indirect active targeting (INTACT) strategy is proposed based on receptor expression disparities between nontarget sites and the targets. By prebinding the antibodies using cell membrane vesicles with appropriate receptor expressions, the INTACT strategy could filter out the interactions on nontarget sites due to their inferior receptor expression, whereas ensure on-demand release at the targets by competitive binding. The strategy is verified on CD47 antibody, realizing drastic alleviation of its clinically concerned hematotoxicity on a series of animal models including humanized patient-derived xenograft platforms, accompanied by preferable therapeutic effects. Furthermore, the INTACT strategy proves extensive applicability for various systems including antibody, antibody-drug conjugate, and targeted delivery systems, providing a potential platform refining the specificity for frontier antibody-related therapies.

A Review on Nano-Approaches Against Periodontitis Treatment

Periodontitis is a provocative condition of the secretions that destroys the alveolar bone, the formation of periodontal pockets, and the degeneration of periodontal ligaments. WHO estimates that between 10 and 15 percent of people worldwide have severe periodontitis. The development of a wide variety of microflora, particularly anaerobes, in the compartments, the release of toxins and enzymes, and the stimulation of the body's immune system are the causes of the disease. Periodontitis was effectively treated using a variety of local or systemic methods. Currently, site-specific delivery, low dose requirements, bypassing first-pass metabolism, a reduction in gastrointestinal side effects, and other factors make the controlled local drug delivery approach preferable to the general approach because it primarily focuses on improving therapeutic outcomes. It offers a safe and efficient way of therapy overall, which improves patient compliance. Various surgical and mechanical procedures completely failed to eradicate the areas' germs. Numerous polymer-based delivery methods, including fibers, films, chips, strips, microparticles, nanoparticles, and nanofibers manufactured from various natural and synthetic materials, have been investigated to successfully transport various medications. These solutions have good mucoadhesion qualities, are Fill the pockets, have high retention at the target site, and are biocompatible and biodegradable. The study gives a general summary of all the different periodontitis targeted delivery systems that are now available and being created.

Aptamer-conjugated gold nanoparticles and their diagnostic and therapeutic roles in cancer.

The burden of incidence rate and mortality of cancer is increasing rapidly, and the development of precise intervention measures for cancer detection and treatment will help reduce the burden and pain of cancer. At present, the sensitivity and specificity of tumor markers such as CEA and CA-125 used clinically are low, while PET, SPECT, and other imaging diagnoses with high sensitivity possess shortcomings, including long durations to obtain formal reports and the inability to identify the molecular pathological type of cancer. Cancer surgery is limited by stage and easy to recur. Radiotherapy and chemotherapy often cause damage to normal tissues, leading to evident side effects. Aptamers can selectively and exclusively bind to biomarkers and have, therefore, gained attention as ligands to be targeted for cancer detection and treatment. Gold nanoparticles (AuNPs) are considered as promising nano carriers for cancer diagnosis and treatment due to their strong light scattering characteristics, effective biocompatibility, and easy surface modification with targeted agents. The aptamer-gold nanoparticles targeting delivery system developed herein can combine the advantages of aptamers and gold nanoparticles, and shows excellent targeting, high specificity, low immunogenicity, minor side effects, etc., which builds a bridge for cancer markers to be used in early and efficient diagnosis and precise treatment. In this review, we summarize the latest progress in the application of aptamer-modified gold nanoparticles in cancer targeted diagnosis and delivery of therapeutic agents to cancer cells and emphasize the prospects and challenges of transforming these studies into clinical applications.

Micro-/Nano-Carboxymethyl Cellulose as a Promising Biopolymer with Prospects in the Agriculture Sector: A Review

The increase in the population rate has increased the demand for safe and quality food products. However, the current agricultural system faces many challenges in producing vegetables and fruits. Indiscriminate use of pesticides and fertilizers, deficiency of water resources, short shelf life of products postharvest, and nontargeted delivery of agrochemicals are the main challenges. In this regard, carboxymethyl cellulose (CMC) is one of the most promising materials in the agriculture sector for minimizing these challenges due to its mechanical strength, viscosity, wide availability, and edibility properties. CMC also has high water absorbency; therefore, it can be used for water deficiency (as superabsorbent hydrogels). Due to the many hydroxyl groups on its surface, this substance has high efficacy in removing pollutants, such as pesticides and heavy metals. Enriching CMC coatings with additional substances, such as antimicrobial, antibrowning, antioxidant, and antisoftening materials, can provide further novel formulations with unique advantages. In addition, the encapsulation of bioactive materials or pesticides provides a targeted delivery system. This review presents a comprehensive overview of the use of CMC in agriculture and its applications for preserving fruit and vegetable quality, remediating agricultural pollution, preserving water sources, and encapsulating bioactive molecules for targeted delivery.

Green synthesis of hyaluronic acid coated, thiolated chitosan nanoparticles for CD44 targeted delivery and sustained release of Cisplatin in cervical carcinoma.

Cervical carcinoma is one of the most prevalent gynecological cancers throughout the world. Cisplatin is used as first line chemotherapy for treatment of cervical cancer, but it comes with plethora of side effects. The aim of this study was to develop hyaluronic acid coated, thiolated chitosan nanocarriers using green synthesis approach, for CD44 targeted delivery and sustained release of Cisplatin in cervical cancer cells. After synthesis through ionic gelation method, Zeta analysis showed that the nanoparticle size was 265.9nm with a zeta potential of +22.3mV and .226 PDI. SEM and TEM analysis confirmed the spherical shape and smooth surface of nanoparticles. FTIR and XRD showed the presence of characteristic functional groups, successful encapsulation of drug, and crystalline nature of nanoparticles respectively. Drug loading and entrapment efficiency were calculated to be 70.1% ± 1.2% and 45% ± .28% respectively. Analysis of in vitro drug release kinetics showed that drug release followed the Higuchi model at pH 6.8 and 7.4 and Cisplatin release for up to 72h confirmed sustained release. In vitro analysis on cervical cancer cells HeLa and normal cervical epithelial cells HCK1T was done through cell morphology analysis, trypan blue assay (concentration range of 10-80μg/ml), and MTT cytotoxic assay (concentration range of 10-90μg/ml). The results showed a higher cytotoxic potential of HA coated, thiolated chitosan encapsulated Cisplatin (HA-ThCs-Cis NP) nanoformulation as compared to pure Cisplatin in HeLa while in HCK1T, pure Cisplatin showed much higher toxicity as compared to HA-ThCs-Cis nanoformulation. These findings suggest that CD44 targeted delivery system can be a useful approach to minimize offtarget toxicities, give sustained release and better cellular uptake in cancer cells.

Investigation of the Therapeutic Effects of Palbociclib Conjugated Magnetic Nanoparticles on Different Types of Breast Cancer Cell Lines.

Drug targeting and controlled drug release systems in cancer treatment have many advantages over conventional chemotherapy in terms of limiting systemic toxicity, side effects, and overcoming drug resistance. In this paper, fabricating nanoscale delivery system composed of magnetic nanoparticles (MNPs) covered with poly-amidoamine (PAMAM) dendrimers and using its advantages were fully used to help the chemotherapeutic drug, Palbociclib, effectively reach tumors, specifically and stay stable in the circulation longer. In order to determine whether conjugate selectivity can be increased for the specific drug type, we have reported different strategies for loading and conjugation of Palbociclib to different generations of magnetic PAMAM dendrimers. The best method leading to the highest amount of Palbociclib conjugation was chosen, and the characterization of the Palbociclib conjugated dendrimeric magnetic nanoparticles (PAL-DcMNPs) were performed. In vitro pharmacological activity of the conjugation was demonstrated by measuring the cell viability and lactate dehydrogenase (LHD) release. Obtained results indicated that PAL-DcMNPs treatment of the breast cancer cell lines, leads to an increase in cell toxicity compared to free Palbociclib. The observed effects were more evident for MCF-7 cells than for MDA-MB231 and SKBR3 cells, considering that viability decreased to 30% at 2.5µM treatment of PAL-DcMNPs at MCF-7 cells. Finally, in Palbociclib and PAL-DcMNPs treated breast cancer cells, the expression levels of some pro-apoptotic and drug resistance related genes were performed by RT-PCR analysis. Our knowledge indicates that the proposed approach is novel, and it can provide new insight into the development of Palbociclib targeting delivery system for cancer treatment.

Targeted Delivery of Sunitinib by MUC-1 Aptamer-Capped Magnetic Mesoporous Silica Nanoparticles

Magnetic mesoporous silica nanoparticles (MMSNPs) are being widely investigated as multifunctional novel drug delivery systems (DDSs) and play an important role in targeted therapy. Here, magnetic cores were synthesized using the thermal decomposition method. Further, to improve the biocompatibility and pharmacokinetic behavior, mesoporous silica was synthesized using the sol-gel process to coat the magnetic cores. Subsequently, sunitinib (SUN) was loaded into the MMSNPs, and the particles were armed with amine-modified mucin 1 (MUC-1) aptamers. The MMSNPs were characterized using FT-IR, TEM, SEM, electrophoresis gel, DLS, and EDX. MTT assay, flow cytometry analysis, ROS assessment, and mitochondrial membrane potential analysis evaluated the nanoparticles' biological impacts. The physicochemical analysis revealed that the engineered MMSNPs have a smooth surface and spherical shape with an average size of 97.6 nm. The biological in vitro analysis confirmed the highest impacts of the targeted MMSNPs in MUC-1 overexpressing cells (OVCAR-3) compared to the MUC-1 negative MDA-MB-231 cells. In conclusion, the synthesized MMSNP-SUN-MUC-1 nanosystem serves as a unique multifunctional targeted delivery system to combat the MUC-1 overexpressing ovarian cancer cells.

Eudragit-coated chitosan-tripterygium glycoside conjugate microspheres alleviate DSS-induced experimental colitis by inhibiting the TLR4/NF-κB signaling pathway

ObjectiveTripterygium glycoside (TG) is a fat-soluble extract of Tripterygium wilfordii, with anti-inflammatory properties associated with TLR signaling pathways. This study constructed a targeted delivery system for experimental colitis, namely, eudragit (EuL)-coated chitosan (Ch)-TG conjugate microspheres (Ch-TG-MS/EuL), and evaluated its therapeutic efficacy and underlying mechanisms. MethodsCh-TG-MS was fabricated using emulsification cross-linking technique and then coated with EuL to create Ch-TG-MS/EuL. Drug release properties were assessed using a dialysis model. Additionally, the therapeutic benefits of Ch-TG-MS/EuL on colonic inflammation and its specific effect on TLR4/NF-κB signaling in intestinal mucosa were evaluated in vivo using a DSS-induced murine colitis model. ResultsThe Ch-TG-MS/EuL microspheres appeared as yellow powders with a slightly enlarged shape, rough surface, and adhesions. The Ch-TG-MS/EuL formulations also exhibited high entrapment efficiency and drug loading rate. High-performance liquid chromatography revealed that Ch-TG-MS/EuL exhibited a less intense peak than free TG, confirming that the drug is contained within the formulation. Free TG displayed explosive release within the first 5 h of administration, while Ch-TG-MS/EuL prevented the pre-mature release of TG and exhibited controllable release up to 24 h. In vivo, noticeable amelioration of intestinal mucosal tissue destruction was achieved with Ch-TG-MS/EuL compared to free TG. Additionally, immunohistochemical and western blotting results revealed that Ch-TG-MS/EuL markedly down-regulated the expression of intestinal mucosal TLR4, MyD88, and NF-κB p65. Hence, Ch-TG-MS/EuL may ameliorate the colon inflammatory response by inhibiting the hyperactivation of TLR4/NF-κB signaling. ConclusionNovel Ch-TG-MS/EuL preparation may represent a colonic delivery system for UC therapeutics by inhibiting TLR4/NF-κB hyperactivation. Data availabilityAll experimental data supporting the conclusions of this study are available from the corresponding author on reasonable request.

Phosphatidylserine-functionalized liposomes-in-microgels for delivering genistein to effectively treat ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory disease involving ulcers in the colon and rectum. The conventional treatments for UC still have many limitations, such as non-specific release, adverse effects and low absorption, resulting in the poor bioavailability of therapeutic agents. To address these challenges, targeting delivery systems are required to specifically deliver drugs to the colonic site with controlled release. Herein, we present a novel microgel oral delivery system, loaded with liposome nanoparticles (Li NPs) containing a natural anti-inflammatory compound genistein (Gen) into alginate microgels, thereby achieving the targeted release of Gen in the colonic region and ameliorating UC symptoms. Initially, Gen was loaded into phosphatidylserine (PS)-functionalized Li NPs to form Gen@Li NPs with an average size of 245.9 ± 9.6 nm. In vitro assessments confirmed that Gen@Li NPs efficiently targeted macrophages and facilitated the internalization of Gen into cells. To prevent rapid degradation in the harsh gastrointestinal tract, Gen@Li NPs were further encapsulated into alginate microgels through electric spraying technology, forming Gen@Li microgels. In vivo distribution tests demonstrated that Gen@Li microgels possessed long-term retention in the colon and gradual release characteristics compared to Gen@Li NPs. Furthermore, in vivo experiments confirmed that Gen@Li microgels significantly alleviated UC symptoms in mice induced by dextran sulfate sodium salt (DSS) mainly through reducing the expression levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and promoting colonic mucosal barrier repair through upregulation of mucosal protein expression. This study shed light on the potential of utilizing oral administration of natural compounds for UC treatment.

Repurposing existing drugs as a therapeutic approach for the prevention of preterm birth.

Preterm birth is the leading cause of perinatal morbidity and mortality; however, current therapies offer limited efficacy to delay birth and improve neonatal outcomes. This review explores the potential of repurposing drugs with known safety profiles to quench uterine contractions and inflammation, identifying promising agents for clinical trials. Preterm birth is the leading cause of neonatal morbidity and mortality globally. Despite extensive research into the underlying pathophysiology, rates of preterm birth have not significantly reduced. Currently, preterm labour management is based on optimising neonatal outcomes. Treatment involves administering drugs (tocolytics) to suppress uterine contractions to allow sufficient time for transfer to an appropriate facility and administration of antenatal corticosteroids for fetal lung maturation. Current tocolytics are limited as they are associated with adverse maternal and fetal effects and only delay delivery for a short period. There has been a serious lack of therapeutic development for preterm birth, and new approaches to protect against or delay preterm birth are urgently needed. Repurposing drugs for the prevention of preterm birth presents as a promising approach by reducing the time and costs associated with pharmaceutical drug development. In this review, we explore the evidence for the potential of therapies, specifically proton pump inhibitors, tumour necrosis factor inhibitors, prostaglandin receptor antagonists, aspirin, and statins, to be repurposed as preventatives and/or treatments for preterm birth. Importantly, many of these innovative approaches being explored have good safety profiles in pregnancy. We also review how delivery of these drugs can be enhanced, either through targeted delivery systems or via combination therapy approaches. We aim to present innovative strategies capable of targeting multiple aspects of the complex pathophysiology that underlie preterm birth. There is an urgent unmet need for preterm birth therapeutic development, and these strategies hold great promise for improving neonatal outcomes.

Nanostructured steady-state nanocarriers for nutrients preservation and delivery.

Food bioactives possess specific physiological benefits of preventing certain diet-related chronic diseases or maintain human health. However, the limitations of the bioactives are their poor stability, lower water solubility and unacceptable bioaccessibility. Structure damage or degradation is often found for the bioactives under certain environmental conditions like high temperature, strong light, extreme pH or high oxygen concentration during food processing, packaging, storage and absorption. Nanostructured steady-state nanocarriers have shown great potential in overcoming the drawbacks for food bioactives. Various delivery systems including solid form delivery system, liquid form delivery system and encapsulation technology have been developed. The embedded food nutrients can largely decrease the loss and degradation during food processing, packaging and storage. The design and application of stimulus and targeted delivery systems can improve the stability, bioavailability and efficacy of the food bioactives upon oral consumption due to enzymatic degradation in the gastrointestinal tract. The food nutrients encapsulated in the smart delivery system can be well protected against degradation during oral administration, thus improving the bioavailability and releazing controlled or targeted release for food nutrients. The encapsulated food bioactives show great potential in nutrition therapy for sub-health status and disease. Much effort is required to design and prepare more biocompatible nanostructured steady-state nanocarriers using food-grade protein or polysaccharides as wall materials, which can be used in food industry and maintain the human health.

Application of nanotechnology in thrombus therapy.

The diseases caused by two pathological processes, thrombosis, and thromboembolism, are clinically known as thrombotic diseases, which seriously threaten human life and health, and their incidence rate is the highest among various diseases. Research on thrombotic diseases is one of the focuses and hotspots of contemporary medical research. Nanomedicine is a new branch of nanotechnology used in the medical field, and nanomaterials are widely used in medical imaging and drug delivery to help diagnose and treat major diseases such as cancer. With the gradual maturity of nanotechnology, new nanomaterials have recently been used in antithrombotic drugs and released accurately at lesions, which has improved antithrombotic therapy safety. Nanosystems can be employed for cardiovascular diagnosis in future as they can aid in diagnosing pathological diseases and treat them with targeted delivery systems. Unlike other reviews, we herein aim to illustrate the progress of nanosystems in thrombosis therapy. This paper mainly describes how a drug-loaded nanosystem can control drug release under various conditions and accurately treat thrombus, summarizing the research progress of nanotechnology in antithrombotic therapy so that clinicians can better understand nanotechnology and its applications and provide new ideas for treating thrombosis.

Molecular Targets of Aptamers in Gastrointestinal Cancers: Cancer Detection, Therapeutic Applications, and Associated Mechanisms.

Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers' generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications.

GLUT1-mediated magnetic liposomes for targeting bone metastatic breast cancer

Bone metastatic breast cancer is a malignant tumor in bone due to the metastasis of breast cancer, and its incidence is increasing worldwide. Treatment of cancer metastasized to bone is still a challenge because of the anticancer drugs lack target specificity. Finding an effective treatment for bone metastasis remains an urgent issue. In order to enhance the delivery of paclitaxel (PTX) to the bone metastases lesions, a novel glucose derivative was designed and synthesized in this work, which was used as liposome ligand to develop the magnetic liposome G-MLip (Glucose-modified magnetic liposome). The liposome could improve the drug formulations in the bone metastases mediated by glucose transporter 1 (GLUT1) and then target cancer cells. The PTX-loaded magnetic liposome PTX-G-MLip was prepared by the film hydration-ultrasound method. And the characterizations, such as size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis, were well evaluated. What’s more, the enhanced target ability was also investigated in vitro and in mice. The metastatic bone-targeted capacity was confirmed that the PTX concentration from PTX-G-MLip in the bone metastases lesions was markedly increased in the presence of magnetic field (MF) compared with the free PTX and other liposomes. Inspired by the enhanced targeting ability, glucose-modified magnetic liposomes could serve as an effective drug delivery system for targeting and treating bone metastases.

Tumor targeted delivery of mycobacterial adjuvant encapsulated chitosan nanoparticles showed potential anti-cancer activity and immune cell activation in tumor microenvironment.

Targeting immunotherapeutics inside the tumor microenvironment (TME) with intact biological activity remains a pressing issue. Mycobacterium indicus pranii (MIP), an approved adjuvant therapy for leprosy has exhibited promising results in clinical trials of lung (NSCLC) and bladder cancer. Whole MIP as well as its cell wall fraction have shown tumor growth suppression and enhanced survival in mice model of melanoma, when administered peritumorally. Clinically, peritumoral delivery remains a procedural limitation. In this study, a tumor targeted delivery system was designed, where chitosan nanoparticles loaded with MIP adjuvants, when administered intravenously showed preferential accumulation within the TME, exploiting the principle of enhanced permeability and retention effect. Bio-distribution studies revealed their highest concentration inside the tumor after 6h of administration. Interestingly, MIP adjuvant nano-formulations significantly reduced the tumor volume in the treated groups and increased the frequency of activated immune cells inside the TME. For chemoimmunotherapeutics studies, MIP nano-formulation was combined with standard dosage regimen of Paclitaxel. Combined therapy exhibited a further reduction in tumor volume relative to either of the MIP nano formulations. From this study a three-pronged strategy emerged as the underlying mechanism; chitosan and Paclitaxel have shown direct role in tumor cell death and the MIP nano-formulation activates the tumor residing immune cells which ultimately leads to the reduced tumor growth.

Developing non-viral or viral vectors for efficient and targeted delivery of genetic material, such as DNA or RNA, for gene therapy applications

Gene therapy has emerged as a promising approach for treating a wide range of genetic and acquired diseases by introducing or modifying genetic material within cells. To achieve successful gene therapy, efficient and precise delivery of genetic material, such as DNA or RNA, to target cells is essential. This abstract explores the development of both non-viral and viral vectors for the delivery of genetic material in gene therapy applications. Non-viral vectors, including lipid nanoparticles (LNPs), polymer-based carriers, and cell-penetrating peptides, have gained significant attention due to their safety profile and ease of production. These vectors are designed to protect genetic material from degradation, facilitate cellular uptake, and release the cargo at the desired location. Recent advancements in nanotechnology have enabled the design of customizable non-viral vectors with enhanced delivery efficiency and reduced offtarget effects. Viral vectors, on the other hand, harness the natural infectivity of viruses to transport genetic material into target cells. Retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses (AAVs) are commonly used viral vectors in gene therapy. Viral vectors offer high transduction efficiency but may trigger immune responses or pose risks of insertional mutagenesis. Efforts in vector engineering have led to the development of safer viral vectors with improved targeting capabilities and reduced immunogenicity. AAVs, in particular, have gained prominence due to their ability to achieve long-lasting gene expression with minimal adverse effects. Targeted delivery strategies aim to enhance vector specificity, ensuring that genetic material reaches the intended cell type or tissue. These strategies include modifying vector surface proteins, employing tissue-specific promoters, or utilizing ligand-receptor interactions. In conclusion, the successful application of gene therapy relies on the development of efficient and targeted delivery systems for genetic material. Non-viral and viral vectors offer distinct advantages and continue to evolve to meet the demands of gene therapy applications. Advances in vector design, safety, and targeting strategies hold promise for the continued progress of gene therapy as a transformative medical intervention.

Pathologically triggered in situ aggregation of nanoparticles for inflammation-targeting amplification and therapeutic potentiation

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated invivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.