Quantitative and high drug loading of self-assembled prodrug with defined molecular structures for effective cancer therapy

Recent advances in self-immolative linkers and their applications in polymeric reporting systems

“…94 Scheme 44 The PEG-based SIE 194 for intracellular delivery of sorafenib as described by Feng and co-workers. 204 Perez has developed a SIE that combines targeting of doxorubicin delivery with a folate unit and a cyclisation-elimination linker that was triggered by intracellular cleavage of a persulfide bond to release the drug. 206 The ethylenediamine-carbamate module has been shown to be highly versatile, and has been used in combination with self-immolative triggers that are activated upon the application of different stimuli (e.g.…”

“…203 The cleavage of disulfide bonds in 194 by cellular thiols has been described by Feng and co-workers as means of controlled release of sorafenib 195 via a cyclisation-elimination event to yield 1,3-oxathiolan-2-one 196 as the by-product via the thiol intermediate 197 (Scheme 44). 204 The drug release system 194 was prepared from multi-armed PEG-NH 2 adding to acrylate 198 to deliver an amphiphilic polymer that exhibited good aqueous solubility and self-assembled into micellar-like nanoparticles (hydrodynamic diameter ca. 150 nm).…”

Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges

“…or cells (e.g., platelet, red blood cells, neutrophils, etc.) as carrier compositions to significantly improve the biocompatibility of TAF-targeting nanoDDSs; (2) employ nanoparticles with porous channels to increase the drug loading capacity and efficiency; (3) utilize the prodrug conjugation strategies to modify the polarity of drugs for better drug/nanocarrier compatibility with higher drug loading. , For optimal efficacy, we shall also consider the impact of the size, , charge, , and shape , of nanoparticles targeting TAFs on their pharmacokinetics, distribution, and uptake into tumor tissues. It has been demonstrated that nanoparticles with smaller sizes (10–200 nm) have a better tumor penetration efficiency, − and slightly negative charge can prolong blood circulation (preventing binding by negatively charged blood proteins).…”

Smart materials for drug delivery and cancer therapy

“…Recently, a GSH‐responsive paclitaxel‐ss‐berberine conjugate was synthetized and self‐assembled to the nanomedicine for synergetic cancer treatment 106 . Tang et al developed a GSH‐responsive amphiphilic dendritic prodrug with quantitative and high drug loading 107 . In this case, sorafenib was attached to the four disulfide‐containing arms of short PEG chain via Michael Addition reaction, and the formative dendritic GSH‐responsive prodrug could self‐assemble into nanoparticles.…”