Stimuli-responsive systems for controlled drug release have been extensively explored in recent years. In this work, we developed a reduction-responsive camptothecin (CPT) nanocapsule (CPT-NC) by combining nanoprecipitation and in situ polymerization using a polymerized surface ligand and a disulfide bond-containing crosslinker. Dissolution rate studies proved that the CPT-NCs have robust drug-release profiles in the presence of glutathione (GSH) owing to the division of the disulfide bond crosslinker which triggers the collapse of the polymer layer. Furthermore, the in vitro investigations demonstrated that the CPT-NCs exhibited a high-cellular uptake efficiency and cytotoxicity for cancer cells of squamous cell carcinoma (SCC-15). Our approach thus presents an effective intracellular drug delivery strategy for anticancer therapy.
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http://dx.doi.org/10.3390/pharmaceutics10040173 | DOI Listing |
Chem Commun (Camb)
January 2023
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, China.
A hierarchically cleaved amphiphile, mPEG-pep-etcSS-CPT, was synthesized to pursue actively targeted cancer therapy through self-assembly. This micelle can respond to MMP-2 achieving dePEGylation and releasing RGD peptides to be internalized into targetable tumor cells. Inside the cell, free CPT could be released by reduction-response leading to cytotoxicity.
View Article and Find Full Text PDFBiomacromolecules
January 2023
Department of Polymer Science and Engineering, School of Chemistry and Chemical Engineering, Hefei University of Technology and Anhui Province Key Laboratory of Advanced Catalytic Materials and Reaction Engineering, Hefei, Anhui 230009, P. R. China.
Multimodal collaborative therapy has been recognized as one of the more effective means to eliminate tumors in the current biomedicine research field as compared with monotherapy. Among them, by taking advantage of its high-precision and controllability, phototherapy has become a mainstay of treatment. However, physical encapsulation of free photosensitive units within nanocarriers was one of the main implementations, which might inevitably result in the photosensitizer leakage and side effect.
View Article and Find Full Text PDFPharmaceutics
June 2022
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
The targeted delivery of drugs to tumor cells and prevention of premature release before reaching the target is one of the key challenges to developing nanomedicines. In this paper, galactose decorated trimethyl chitosan (GT)-camptothecin (CPT) prodrug nanoparticles (GT-ss-CPT NPs) were prepared from GT-CPT conjugates linked by dithiodipropionic acid. The obtained GT-ss-CPT NPs were spherical with a particle size of 184.
View Article and Find Full Text PDFMol Pharm
September 2022
School of Chemistry and Chemical Engineering, Chongqing University, 174 Shazheng Street, Chongqing 400044, P. R. China.
Fabrication of self-delivery drug systems can surmount low drug bioavailability and achieve a precise therapeutic process. In this study, a hydrogen sulfide-responsive (HS) small molecule prodrug was synthesized by linking two chemotherapy drugs, camptothecin (CPT) and gemcitabine (GT), using a reductive disulfide bond simultaneously with a lock GT strategy using a HS-responsive azide group (denoted as N-GT-CPT). The ingenious design endows the easy coprecipitation peculiarity of the prodrug with clinical indocyanine green (ICG) via a combined interaction force of hydrophobic, π-π stacking, and electrostatic interactions of anions and cations, thus producing a more stable and multifunctional therapeutic nanosystem.
View Article and Find Full Text PDFACS Omega
June 2022
College of Chemistry, Chemical Engineering and Materials Science, State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Suzhou Key Laboratory of Macromolecular Design and Precision Synthesis, Soochow University, Suzhou 215123, P. R. China.
To overcome the limitation of conventional nanodrugs in tumor targeting efficiency, coupling targeting ligands to polymeric nanoparticles can enhance the specific binding of nanodrugs to tumors. Cyclo(Arg-Gly-Asp-d-Phe-Lys) (abbreviated as c(RGDfK)) peptide has been widely adopted due to its high affinity to the tumor marker αβ integrin receptor. In this study, we develop a cRGD peptide-conjugated camptothecin (CPT) prodrug, which enables self-assembly of nanoparticles for precise targeting and enrichment in tumor tissue.
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