Reversal of doxorubicin resistance by branched star porphyrin-polylactide composed nanoparticle in cancer cells
Date Issued
2009
Date
2009
Author(s)
Huang, Ling-Yi
Abstract
One potential way to overcome the side effects of chemotherapy is to develop therapeutic drug delivery systems that enhance tumor cytotoxicity but reduce the adverse effects to the normal cells. Recently the studies of nanoparticle formulation of anticancer devices via drugs associated with synthetic polymers have been used as delivery systems for this purpose. Because of enhanced permeability and retention effects, polymer-drug conjugates with nano-sizes can more easily permeate tumor tissues and accumulate in the tumor microenvironment over time. In this study, we attempt to synthesize a novel star-shaped biodegradable polylactide (PLA) with photodynamic and chemo- therapeutics for cancer treatments. The branched star porphyrin-PLA conjugate was synthesized successfully by ring-opening polymerization of lactides from porphyrins with benzyl alcohol under a novel [(DAIP)2Ca]2 catalyst as the red polymer powder. The doxorubicin-loaded nanoparticles were fabricated by a modified oil-in-water single-emulsion solvent evaporation/extraction technique. The size of branched star porphyrin-PLA composed nanoparticle (BSPPLA-NP) without or with dug loading was 67.26nm or 79.7nm, respectively. his novel BSPPLA-NP was characterized for intracellular distribution, cell viability and phototoxicity in vitro. The results show that BSPPLA-NP, mainly localized in endosome/lysosome compartments, was non-toxic below 10μM, but significantly induced cell death after suitable irradiation (1.4J/cm2) in HeLa cells and MCF-7 cells. Furthermore, the photodynamic treatment obviously improved the cytotoxicity of doxorubicin-loaded BSPPLA-NP through synergistic effects by median effect analysis. Therefore, the BSPPLA-NP with an efficient chemotherapeutic agents loading, showed considerable potential as a bimodal biomaterial for chemo-photodynamic drug delivery system for cancer therapy.o solve the drug resistant problem used TPGS, a water-soluble vitamin E derivative that can inhibit P-glycoprotein and also a good surfactant. PCI (photochemical internalization) that combined with BSPPLA-NP and doxorubicin is the other way to reverse drug resistant.
Subjects
Polylactide
Porphyrin
Doxorubicin
Nanoparticles
Photodynamic therapy
Chemotherapy
P-glycoprotein
Drug resistance
SDGs
Type
thesis
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