A Co-delivery System Based on a Dimeric Prodrug and Star-Shaped Polymeric Prodrug Micelles for Drug Delivery

Abstract

Chemotherapy is one of the commonly used therapies for the treatment of malignant tumors. Insufficient drug-loading capacity is the major challenge for polymeric micelle–based drug delivery systems of chemotherapy. Here, the redox-responsive star-shaped polymeric prodrug (PSSP) and the dimeric prodrug of paclitaxel (PTX) were prepared. Then the dimeric prodrug of PTX (diPTX, diP) was loaded into the core of the star-shaped polymeric prodrug micelles of PSSP by hydrophobic interaction forming the redox-responsive prodrug micelles of diPTX@PSSP for intracellular drug release in tumor cells. The hydrodynamic diameter of diPTX@PSSP nanoparticles was 114.3 nm ± 2.1 (PDI = 0.219 ± 0.016), and the micelles had long-term colloidal stability and the drug-loading content (DLC) of diPTX and PTX is 16.7 and 46.9%, respectively. The prepared micelles could broke under the reductive microenvironment within tumor cells, as a result, the dimeric prodrug of diP and polymeric prodrug micelles of PSSP were rapidly disassembled, leading to the rapid release of intracellular drugs. In vitro release studies showed that under the condition of reduced glutathione (GSH) (10 mM), the release of PTX was significantly accelerated with approximately 86.6% released within 21 h, and the released PTX in cytoplasm could promote the disintegration of microtubules and induce cell apoptosis. These results indicated that the new type of this reduction-sensitive nanodrug delivery system based on dimeric prodrug@polymeric prodrug micelles would be a promising technology in chemotherapy.

HSA-nanobinders crafted from bioresponsive prodrugs for combined cancer chemoimmunotherapy–an in vitro exploration

“…For the preparation of nanobinders (NBs), several parameters must be thoughtfully considered, including their stability over time, the percentage of tEB functionalization to allow proper binding with HSA, and the Nlg/Ptx ratio, which should be in favor of Nlg ( Sonpavde et al, 2020 ). Moreover, it is established that homodimeric disulfide prodrugs, such as Nlg dimer, i.e., NlgD ( Figure 1 ; Supplementary Material ), ( Feng et al, 2018 ) can enhance the stability of prodrug-based nanoassemblies and facilitate the reduction-responsive release of active drugs ( Zhou et al, 2021 ; Liu et al, 2022 ; Zhong et al, 2023 ). Therefore, to achieve greater flexibility in the composition of NBs concerning stability and drug ratio, we chose to synthesize a monomeric HSA-binding analogue of Nlg, i.e., nMAC ( Scheme 3 ), to be combined with pMACs and NlgD (see § 3.4).…”

Recent advances in NIR-II fluorescence based theranostic approaches for glioma

“…Drug delivery systems are used to deliver drugs to the desired tissues and organs, and allow for controllable drug release by multifunctional drug carriers ( Li N. et al, 2019 ; Zhang Y. et al, 2022 ). Drug delivery can solve many existing problems that limit the use of therapeutic drugs, such as poor solubility, lack of biodistribution and bioavailability, low selectivity, and side effects ( Liu et al, 2015 ; Liu D. et al, 2018 ; Huang X. et al, 2021 ; Wei et al, 2021 ; Zhou et al, 2021 ; Kalot et al, 2022 ). Recently, NIR fluorophore-functionalized delivery systems targeting gliomas have been developed that allow the visualization of the delivery process and monitoring of drug behavior.…”

Biomimetic Exosomes: A New Generation of Drug Delivery System

“…Among them, nanotechnology was introduced into medicine and, therefore, improved treatment. Various synthetic nanoparticles, such as liposomes ( Sur et al, 2014 ; Dammes et al, 2021 ), micelles ( Gong et al, 2012 ; Kataoka et al, 2012 ), and self-assembled peptides ( Cully, 2015 ; Worthington et al, 2017 ), and inorganic materials, such as graphene ( Xiaoming et al, 2008 ; Panwar et al, 2019 ) and graphene-like 2D materials ( Huang et al, 2021 ), are used to carry different cargo ( Kuang et al, 2020 ; Zhou et al, 2021 ). Over the past few decades, nanocarriers for drug delivery have found applications in clinical use ( Wicki et al, 2015 ; Min et al, 2015 ).…”