Nanoparticles for Delivering Natural Product Chemotherapeutics to Breast Cancer Cells

Pullan, Jessica E.; Mamnoon, Babak; Kale, Narendra; Mallik, Sanku

doi:10.1016/b978-0-12-821277-6.00010-6

Cited by 1 publication

(2 citation statements)

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“…Nanomedicine and nanotechnology are emerging fields in drug delivery, diagnosis, and the development of nanoscale materials for cancer therapy. − Nanocarrier-based drug delivery systems can address the shortcomings of traditional chemotherapy by improving circulation half-life, tumor penetration, and cellular internalization. , Among various nanoparticles, polymersomes show considerable promise to deliver drugs into cancerous tissues . They are self-assembled bilayer vesicles prepared from amphiphilic copolymers with hydrophilic and hydrophobic blocks. − Vesicle formation is favored when the molecular weight ratio of the hydrophilic block to the whole polymer is between 20 to 40%. ,, Polymersomes carry hydrophilic drugs within the aqueous core and hydrophobic drugs inside the bilayer simultaneously. , Poly(ethylene glycol) (PEG) is commonly used as a hydrophilic block due to its biocompatibility, reduction in plasma protein adsorption, and the resultant prolonged circulation time of the polymersomes …”

Section: Introductionmentioning

confidence: 99%

“…21,22 Among various nanoparticles, polymersomes show considerable promise to deliver drugs into cancerous tissues. 23 They are self-assembled bilayer vesicles prepared from amphiphilic copolymers with hydrophilic and hydrophobic blocks. 24−26 Vesicle formation is favored when the molecular weight ratio of the hydrophilic block to the whole polymer is between 20 to 40%.…”

Section: Introductionmentioning

confidence: 99%

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Targeting Estrogen Receptor-Positive Breast Microtumors with Endoxifen-Conjugated, Hypoxia-Sensitive Polymersomes

Mamnoon

Froberg

et al. 2021

ACS Omega

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Endoxifen is the primary active metabolite of tamoxifen, a nonsteroidal-selective estrogen receptor modulator (SERM) and widely used medication to treat estrogen receptor-positive (ER+) breast cancer. In this study, endoxifen was conjugated to the surface of polymeric nanoparticles (polymersomes) for targeted delivery of doxorubicin (DOX) to estrogen receptor-positive breast cancer cells (MCF7). Rapid cell growth and insufficient blood supply result in low oxygen concentration (hypoxia) within the solid breast tumors. The polymersomes developed here are prepared from amphiphilic copolymers of polylactic acid (PLA) and poly(ethylene glycol) (PEG) containing diazobenzene as the hypoxia-responsive linker. We prepared two nanoparticle formulations: DOX-encapsulated hypoxia-responsive polymersomes (DOX-HRPs) and endoxifen-conjugated, DOX-encapsulated hypoxia-responsive polymersomes (END-DOX-HRPs). Cellular internalization studies demonstrated eight times higher cytosolic and nuclear localization after incubating breast cancer cells with END-DOX-HRPs (targeted polymersomes) in contrast to DOX-HRPs (nontargeted polymersomes). Cytotoxicity studies on monolayer cell cultures exhibited that END-DOX-HRPs were three times more toxic to ER+ MCF7 cells than DOX-HRPs and free DOX in hypoxia. The cell viability studies on three-dimensional hypoxic cultures also demonstrated twice as much toxicity when the spheroids were treated with targeted polymersomes instead of nontargeted counterparts. This is the first report of surface-decorated polymeric nanoparticles with endoxifen ligands for targeted drug delivery to ER+ breast cancer microtumors. The newly designed endoxifen-conjugated, hypoxia-responsive polymersomes might have translational potential for ER+ breast cancer treatment.

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