Enhanced Paclitaxel Efficacy to Suppress Triple-Negative Breast Cancer Progression Using Metronomic Chemotherapy with a Controlled Release System of Electrospun Poly-d-l-Lactide-Co-Glycolide (PLGA) Nanofibers

Abstract

Triple-negative breast cancer (TNBC) is highly aggressive and responds poorly to conventional chemotherapy. The challenge of TNBC therapy is to maximize the efficacies of conventional chemotherapeutic agents and reduce their toxicities. Metronomic chemotherapy using continuous low-dose chemotherapy has been proposed as a new treatment option, but this approach is limited by the selection of drugs. To improve antitumor therapeutic effects, we developed electrospun paclitaxel-loaded poly-d-l-lactide-co-glycolide (PLGA) nanofibers as a topical implantable delivery device for controlled drug release and site-specific treatment. The subcutaneously implanted paclitaxel-loaded nanofibrous membrane in mice was compatible with the concept of metronomic chemotherapy; it significantly enhanced antitumor activity, inhibited local tumor growth, constrained distant metastasis, and prolonged survival compared with intraperitoneal paclitaxel injection. Furthermore, under paclitaxel-loaded nanofiber treatment, systemic toxicity was low with a persistent increase in lean body weight in mice; in contrast, body weight decreased in other groups. The paclitaxel-loaded nanofibrous membranes provided sustained drug release and site-specific treatment by directly targeting and changing the tumor microenvironment, resulting in low systemic toxicity and a significant improvement in the therapeutic effect and safety compared with conventional chemotherapy. Thus, metronomic chemotherapy with paclitaxel-loaded nanofibrous membranes offers a promising strategy for the treatment of TNBC.

Antiviral Drug 2-thio-6-azauridine Sensitizes Paclitaxel-Resistant Triple Negative Breast Cancer Cells by Targeting Mammosphere Formation and ABC Transporters

“…33 PTX with various combinations has been evaluated in patients with TNBC. [33][34][35][36][37][38][39] Co-delivery of PTX and cisplatin using hydrogel showed synergistic effect on MDA-MB-231 cells by inducing apoptosis. 40 A recent clinical trial has reported on the use of PTX with the combination of targeted agents, 41 which disrupt microtubules, 42 induce DNA damage, 43 inhibit cell cycle, 44 induce apoptosis, 45 and reduce angiogenesis.…”

A Review of the Release Profiles and Efficacies of Chemotherapy Drug-Loaded Electrospun Membranes

“…Electrospun membranes should be designed to largely enhance their release quantity over the polymer degradation period and act as carriers to increase their compatibility with an aqueous environment. PLA, PLGA 50:50, and PCL electrospun membranes could achieve logistic release of more than 50% encapsulated PTX or cisplatin for 30 days or longer [ 60 , 63 , 67 , 68 , 71 , 87 , 89 ]. Complex encapsulation techniques like conjugation [ 59 ], dextran encapsulation [ 87 ], blending with chitosan [ 60 ], and release enhancers [ 71 ] were effective in boosting release efficiency (released drug ratio).…”

LncRNA H19 Impairs Chemo and Radiotherapy in Tumorigenesis

“…Mechanistically, PTX action includes several signaling pathways in which PTX modulates cellular processes that results in programmed cell death triggering. PTX is considered as the first-line treatment drug in breast cancer (BC), especially in triple negative breast cancer (TNBC) [ 56 ], since this subtype of carcinoma is not sensitive to estrogen receptor positive breast cancer cell. Unfortunately, the resistance of BC to PTX treatment is a great obstacle in clinical applications and one of the major causes of death associated with treatment failure.…”