pH and Redox Dual Responsive Nanoparticle for Nuclear Targeted Drug Delivery

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• 作者：Remant Bahadur K. C. ; Bindu Thapa ; Peisheng Xu
• 刊名：Molecular Pharmaceutics
• 出版年：2012
• 出版时间：September 4, 2012
• 年：2012
• 卷：9
• 期：9
• 页码：2719-2729
• 全文大小：544K
• 年卷期：v.9,no.9(September 4, 2012)
• ISSN：1543-8392

文摘

To mimic the clinic dosing pattern, initially administering high loading dose and then low maintenance dose, we designed a novel poly(2-(pyridin-2-yldisulfanyl)ethyl acrylate) (PDS) based nanoparticle delivery system. Side chain functional PDS was synthesized by free radical polymerization. Polyethylene glycol and cyclo(Arg-Gly-Asp-class="smallcaps">d-Phe-Cys) (cRGD) peptide was conjugated to PDS through thiol鈥揹isulfide exchange reaction to achieve RPDSG polymer. RPDSG/DOX, RPDSG nanoparticle loaded with doxorubicin, was fabricated by cosolvent dialysis method. The size of the nanoparticles was 50.13 卤 0.5 nm in PBS. The RPDSG/DOX nanoparticle is stable in physiological condition while quickly releasing doxorubicin with the trigger of acidic pH and redox potential. Furthermore, it shows a two-phase release kinetics, providing both loading dose and maintenance dose for cancer therapy. The conjugation of RGD peptide enhanced the cellular uptake and nuclear localization of the RPDSG/DOX nanoparticles. RPDSG/DOX exhibits IC₅₀ close to that of free doxorubicin for HCT-116 colon cancer cells. Due to the synergetic effect of RGD targeting effect and its two-phase release kinetics, RPDSG/DOX nanoparticles display significantly higher anticancer efficacy than that of free DOX at concentrations higher than 5 渭M. These results suggest that RPDSG/DOX could be a promising nanotherapeutic for tumor-targeted chemotherapy.

Keywords:

cs.org/action/doSearch?action=search&searchText=drug+delivery&qsSearchArea=searchText">drug delivery; cs.org/action/doSearch?action=search&searchText=doxorubicin&qsSearchArea=searchText">doxorubicin; cs.org/action/doSearch?action=search&searchText=nanoparticles&qsSearchArea=searchText">nanoparticles; cs.org/action/doSearch?action=search&searchText=pH+responsive&qsSearchArea=searchText">pH responsive; cs.org/action/doSearch?action=search&searchText=redox+responsive&qsSearchArea=searchText">redox responsive; cs.org/action/doSearch?action=search&searchText=nuclear+targeted+drug+delivery&qsSearchArea=searchText">nuclear targeted drug delivery