Paclitaxel prodrug nanoparticles boost antitumor efficacy via hitchhiking of human serum albumin.

Improving drug delivery efficacy is the key point for enhancing the therapeutic index of medicines. Herein, we report fatty chain conjugated paclitaxel (PTX) prodrugs with a disulfide bond as linker. The formed prodrugs can self-assemble into stable nanoparticles in aqueous solutions, and rapidly transform into long-circulating nanocomplexes via the non-covalent binding to serum albumin in blood, enabling efficient drug delivery and robust antitumor effect.

Paclitaxel Prodrug Enables Glutathione Depletion to Boost Cancer Treatment.

Herein, we constructed a paclitaxel (PTX) prodrug (PA) by conjugating PTX with acrylic acid as a cysteine-depleting agent. The as-synthesized PA can assemble with diacylphosphatidylethanolamine-PEG to form stable nanoparticles (PA NPs). After endocytosis into cells, PA NPs can specifically react with cysteine and trigger release of PTX for chemotherapy.

Ferrocene-Conjugated Paclitaxel Prodrug for Combined Chemo-Ferroptosis Therapy of Cancer.

Herein, we developed a paclitaxel prodrug (PSFc) through the conjugation of paclitaxel (PTX) and ferrocene a redox-responsive disulfide bond. PSFc displays acid-enhanced catalytic activity of Fenton reaction and is capable of forming stable nanoparticles (PSFc NPs) through the assembly with distearoyl phosphoethanolamine-PEG. After being endocytosed, PSFc NPs could release PTX to promote cell apoptosis in response to overexpressed redox-active species of tumor cells.

Indocyanine green potentiated paclitaxel nanoprodrugs for imaging and chemotherapy.

Self-assembled prodrug nanoparticles with tumor-responsive capacity have great potential in tumor visualization and treatment. However, the nanoparticle formulas usually contain multiple components, especially polymeric materials, which result in various potential issues. Herein, we report an indocyanine green (ICG)-driven assembly of paclitaxel prodrugs integrating near-infrared fluorescence imaging and tumor-specific chemotherapy.

A Paclitaxel Prodrug with Copper Depletion for Combined Therapy toward Triple-Negative Breast Cancer.

Tuning the content of copper is of great significance for the treatment of cancer and neurodegenerative diseases. Herein, we synthesized a redox-responsive paclitaxel (PTX) prodrug by conjugating PTX with a copper chelator through a disulfide bond. The as-fabricated prodrug (PSPA) showed specific chelation toward copper ions and could assemble with distearoyl phosphoethanolamine-PEG to form stable nanoparticles (PSPA NPs) in aqueous media.

Carboxylated paclitaxel prodrug nanofibers for enhanced chemotherapy.

The facile availability of nanoformulations with enhanced antitumor performance remains a big challenge. Herein, we synthesize paclitaxel prodrugs with amphiphilic structures and robust assembling ability. Carboxylated paclitaxel prodrugs (PSCB) containing disulfide bonds prefer to form exquisite nanofibers, while phenylcarbinol end capped paclitaxel prodrugs (PSP) assemble into spherical nanoparticles.

Hypoxia-Activated PEGylated Paclitaxel Prodrug Nanoparticles for Potentiated Chemotherapy.

Developing controlled drug-release systems is imperative and valuable for increasing the therapeutic index. Herein, we synthesized hypoxia-responsive PEGylated (PEG = poly(ethylene glycol)) paclitaxel prodrugs by utilizing azobenzene (Azo) as a cleavable linker. The as-fabricated prodrugs could self-assemble into stable nanoparticles (PAP NPs) with high drug content ranging from 26 to 44 wt %.

Deep Tumor Penetrating Gold Nano-Adjuvant for NIR-II-Triggered In Situ Tumor Vaccination.

Local tumor photothermal treatment with the near-infrared light at the second window (NIR-II) is a promising strategy in triggering the in situ tumor vaccination (ISTV) for cancer therapy. However, limited penetration of photothermal agents within tumors seriously limits their spatial effect in generating sufficient tumor-associated antigens, a key factor to the success of ISTV. In this study, a nano-adjuvant system is fabricated based on the NIR-II-absorbable gold nanostars decorated with hyaluronidases and immunostimulatory oligodeoxynucleotides CpG for ISTV.

Intracellular Enzyme-Responsive Profluorophore and Prodrug Nanoparticles for Tumor-Specific Imaging and Precise Chemotherapy.

Responsive drug delivery systems possess great potential in disease diagnosis and treatment. Herein, we develop an activatable prodrug and fluorescence imaging material by engineering the endogenous NAD(P)H:quinone oxidoreductase-1 (NQO1) responsive linker. The as-prepared nanomaterials possess the NQO1-switched drug release and fluorescence enablement, which realizes the tumor-specific chemotherapy and imaging in living mice.

Fluorinated paclitaxel prodrugs for potentiated stability and chemotherapy.

Robust colloidal stability is an essential prerequisite for effective drug delivery. Herein, a series of fluorinated paclitaxel prodrugs bridged with redox-responsive linkages were synthesized, and the effect of fluorination on the assembly behavior and physiological stability was investigated. The 17-fluorinated ethanol-modified paclitaxel prodrug could self-assemble into stable nanoparticles without the addition of any surfactants.

Engineering Paclitaxel Prodrug Nanoparticles via Redox-Activatable Linkage and Effective Carriers for Enhanced Chemotherapy.

The current clinical performance of chemotherapy is far from satisfactory, greatly limited by insufficient delivery efficacy and serious systemic side effects. Dimeric prodrug systems are emerging as valuable strategies for boosting the antitumor outcome. Here, dimeric paclitaxel prodrugs were synthesized with different bridged linkers, and the formed prodrug nanoparticles possessed excellent colloidal stability and ultrahigh drug content.