Doxorubicin and resveratrol co-delivery nanoparticle to overcome doxorubicin resistance

Abstract

With the extensive application of doxorubicin (DOX), DOX resistance has become one of the main obstacles to the effective treatment of breast cancer. In this paper, DOX and resveratrol (RES) were co-encapsulated in a modified PLGA nanoparticle (NPS) to overcome the DOX resistance. CLSM results indicated that DOX and RES were simultaneously delivered into the nucleus of DOX-resistant human breast cancer cells by DOX/RES-loaded NPS. Consequently, DOX/RES-loaded NPS showed significant cytotoxicity on MDA-MB-231/ADR cells and MCF-7/ADR cells. Furthermore, DOX/RES-loaded NPS could overcome DOX resistance by inhibiting the expression of drug resistance-related protein such as P-gp, MRP-1 and BCRP, and induce apoptosis through down-regulating the expression of NF-κB and BCL-2. In tumor-bearing mice, DOX/RES-loaded NPS mainly delivered DOX and RES to tumor tissue. Compared with free DOX, DOX/RES-loaded NPS significantly inhibited the DOX-resistant tumor growth in tumor-bearing mice without causing significant systemic toxicity. In a word, DOX/RES-loaded NPS could overcome the DOX resistance and had the potential in the treatment of DOX-resistant breast cancer.

Synthesis and Characterization of cryogel microcarriers for sustained local delivery of anticancer therapeutics to Glioblastoma multiforme

“…Pharmacokinetic analysis of amphiphilic compounds reveal predisposition of self-aggregation, that often leads to an undesirable initial burst-release, which was also the case in this study too, as drug particles, bound to the outer surface of the drug carrier, dissociate altogether (Fülöp et al 2013;Zhao et al 2016). Densely coating the microcarriers is realized as one way of reducing the burst release rate, though the proportion of SPA incorporation in the microcarriers would become much more restricted (Suk and Xu 2017).…”

Resveratrol and Its Nanoformulation Attenuate Growth and the Angiogenesis of Xenograft and Orthotopic Colon Cancer Models

“…This could be interpreted as enhancing the bioavailability of RSV by nanoformulation. Similarly, Zhao et al [15] stated that Dox and RSV co-encapsulated in modified PLGA NPs significantly inhibited Dox-resistant tumor growth in MDA-MB-231 and MCF-7 tumor-bearing mice without causing significant systemic toxicity. Moreover, RSV nanocomposite had a high anticancer efficacy against mouse colon cancer cells CT26 in vitro and in a xenograft mouse model with less tissue toxicity [35].…”

“…Generally, we recommend using NP-RSV as a therapeutic to control colon cancer.Numerous studies have showed an enhancement in the bioavailability of RSV by nanoformulations and an increase in the sensitivity of cancer cells to chemotherapy. Zhao et al [15] found an increase in the sensitivity of breast cancer-bearing mice to co-delivery of doxorubicin (Dox) and RSV via poly glyco-lactic acid (PLGA) nanoparticles (NPs) to overcome Dox resistance. Moreover, RSV oral bioavailability was increased 10 times when loaded in casein NPs [16].…”

<p>Doxorubicin Delivered Using Nanoparticles Camouflaged with Mesenchymal Stem Cell Membranes to Treat Colon Cancer</p>

“…Free DOX accumulates in the nucleus because the molecules enter cells via the free diffusion pathway, and are quickly transferred to the nucleus, where they strongly bind to chromosomal DNA. 31,32 In contrast, DOX-loaded NPs are taken up via endocytosis and accumulate in the lysosomes, where the nanocarriers degrade and drug release occurs. 33 Overall, DOX-SPIO cellular uptake efficiency was significantly improved by surface modification with MSC membranes.…”