pH-Sensitive nanoparticles based on amphiphilic imidazole/cholesterol modified hydroxyethyl starch for tumor chemotherapy

Recent advances in pH/enzyme-responsive polysaccharide-small-molecule drug conjugates as nanotherapeutics.

Diselenide-triggered hydroxyethyl starch conjugate nanoparticles with cascade drug release properties for potentiating chemo-photodynamic therapy.

Virus-like particles (VLPs) have natural structural antigens similar to those found in viruses, making them valuable in vaccine immunization. Furthermore, VLPs have demonstrated significant potential in drug delivery, and emerged as promising vectors for transporting chemical drug, genetic drug, peptide/protein, and even nanoparticle drug. With virus-like permeability and strong retention, they can effectively target specific organs, tissues or cells, facilitating efficient intracellular drug release. Further modifications allow VLPs to transfer across various physiological barriers, thus acting the purpose of efficient drug delivery and accurate therapy. This article provides an overview of VLPs, covering their structural classifications, deliverable drugs, potential physiological barriers in drug delivery, strategies for overcoming these barriers, and future prospects. 

Overcoming biological barriers by virus-like drug particles for drug delivery.

Continuous drug delivery modification is the scientific approach and is a basic need for the efficient therapeutic efficacy of active drug molecules. Polymer-drug conjugates have long been a hallmark of the drug delivery sector, with various conjugates on the market or in clinical trials. Improved drug solubilization, extended blood circulation, decreased immunogenicity, controlled release behavior, and increased safety are the advantages of conjugating drugs to the polymeric carrier like polyethylene glycol (PEG). Polymer therapies have evolved over the last decade, resulting in polymer-drug conjugates with diverse topologies and chemical properties. Traditional nondegradable polymeric carriers like PEG and hydroxy propyl methacrylate have been clinically employed to fabricate polymer-drug conjugates. Still, functionalized polymer-drug conjugates are increasingly being used to increase localized drug delivery and ease of removal. Researchers have developed multifunctional carriers that can "see and treat" patients using medicinal and diagnostic chemicals. This review focused on the various conjugation approaches for attaching the doxorubicin to different polymers to achieve enhanced therapeutic efficacy, that is, increased bioavailability and reduced adverse effects.

Doxorubicin Conjugates: An Efficient Approach for Enhanced Therapeutic Efficacy with Reduced Side Effects.

Background Chemotherapeutic drugs used for tumor treatments often show limited efficiency due to their short lifetime, nonspecific delivery, and slow or insufficient intracellular drug release, and also, they can cause severe system or organ toxicity. The development of chemotherapeutic nanomedicines with high efficacy and satisfactory safety still remains a challenge for current tumor chemotherapy. Methods A novel type of conjugate was synthesized using hydroxyethyl starch (HES) as a carrier while binding doxorubicin (DOX) onto HES backbone through a pH/redox responsive linker containing both disulfide and hydrazone bonds in series. The built conjugates were self-assembled into nanoparticles (NPs) (HES-SS-hyd-DOX NPs) for achieving enhanced antitumor therapy and adequate safety. Results HES-SS-hyd-DOX NPs had a certain ability for the tumor-orientated drug accumulation and were capable of releasing DOX itself rather than DOX derivatives. It was found that the pH/redox responsive linkage enabled the NPs to achieve fast and sufficient intracellular drug release. Based on the tumor-bearing mouse model, antitumor results demonstrated that these NPs were able to inhibit the growth of the advanced tumors with significantly enhanced efficacy when compared to free DOX, and to those conjugate NPs containing only a single responsive or unresponsive bond. Besides, HES-SS-hyd-DOX NPs also showed adequate safety to the normal organs of the treated mice. Conclusion The pH/redox responsive linkage in HES-SS-hyd-DOX was found to play a critical role in mediating the drug accumulation and the fast and sufficient intracellular drug release. The HES-exposed surface of HES-SS-hyd-DOX NPs endowed the NPs with long circulation capability and remarkably reduced the DOX-induced side effects.

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Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy.

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Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy.