Self-Assembly Engineering Nanodrugs Composed of Paclitaxel and Curcumin for the Combined Treatment of Triple Negative Breast Cancer

Abstract

The clinical outcomes of triple-negative breast cancer (TNBC) chemotherapy are unsatisfactory. Water solubility and biosafety of chemo drugs are also major barriers for achieving satisfactory treatment effect. In this study, we have reported a combinational strategy by self-assembly engineering nanodrugs PC NDs, which were composed of paclitaxel (PTX) and curcumin (Cur), for effective and safe TNBC chemotherapy. PC NDs were prepared through reprecipitation method without using any additional carriers. The PC NDs were preferentially taken up by TNBC cells and we also observed pH-related drug release. Compared with free PTX and simple PTX/Cur mixture, PC NDs have shown higher therapeutic efficiency and better prognosis while the metastasis rate was significantly lower than that of either PTX or PTX/Cur mix group. Therefore, the self-assembly engineered PC NDs might be a promising nanodrugs for efficient and safe TNBC chemotherapy.

HSA-Binding Prodrugs-Based Nanoparticles Endowed with Chemo and Photo-Toxicity against Breast Cancer

“…These data are in agreement with literature reports accounting for a limited efficacy of PTX on in vitro 4T1 cells [ 49 , 50 ] and on primary 4T1 tumor models [ 51 ].…”

“…To exclude that the scarce cytotoxic response to nanoparticles was due to an inefficient prodrug's activation in 4T1 cells, we assessed the cytotoxicity of free PTX formulated in standard conditions (e.g., DMSO), showing very limited efficacy, and comparable to that exerted by our nanosystems (Figure S12). These data are in agreement with literature reports accounting for a limited efficacy of PTX on in vitro 4T1 cells [49,50] and on primary 4T1 tumor models [51].…”

“…Combination therapy in the absence (Figures S15 and S16) and in the presence of light (Figures 9 and 10) was performed in the three-dimensional in vitro models maintaining unaltered the incubation and irradiation protocol used with cell monolayers, and by assessing cell viability reduction through ATP level measurement (e.g., 3D Glo Assay) 24 or 48 h after irradiation. As expected, and in agreement with the results obtained in cells monolayers, 4T1 spheroids showed extreme resistance toward PTX formulations treatment [49][50][51] at both time points (Figure 9), whereas Pba activation with red light showed a progressive and dose-dependent loss of viability. As visible from graphs of Figure 9a,b and Table S4, reporting the IC 50 values of the different formulations, MAL-PTX 2 S@Pba treatment did not significantly improve cell killing efficiency with respect to BOC-PTX 2 S@Pba, whereas free Pba showed the lowest IC 50 value, in agreement to its higher uptake (Figure 8a).…”

Recent Advances in Stimuli-Sensitive Amphiphilic Polymer-Paclitaxel Prodrugs

“…It is a natural substance derived from the needles and bark of the Pacific yew tree. It is a mitotic inhibitor used primarily in cancer chemotherapy, which can be used in the treatment of various cancers, including ovarian cancer, esophagus cancer, small and non–small-cell lung cancer, multiple myeloma cancer, bladder cancer, breast cancer, head and neck cancer, colon cancer, and Kaposi’s sarcoma ( Khalifa et al, 2019 ; Chen et al, 2021 ; Peng et al, 2021 ; Zuo et al, 2021 ). PTX is a microtubule stabilizing drug, which can prevent cytoskeletal microtubules from depolymerizing into free tubulin.…”

Fabrication of Ginsenoside-Based Nanodrugs for Enhanced Antitumor Efficacy on Triple-Negative Breast Cancer

“…Recently, carrier-free drug delivery systems, fabricated by self-assembly or co-assembly of pure drug molecules, have attracted substantial attention (Qin et al, 2017;Mei et al, 2022). Pure drug molecules without any chemical modification can spontaneously form uniform NPs by employing several methods Sun et al, 2019;Zuo et al, 2021). Compared with free drugs, carrier-free nanodrugs afford improved bioavailability, prolonged blood circulation times, and superior tumor accumulation (Zheng et al, 2021).…”