Co-encapsulation of curcumin and doxorubicin in albumin nanoparticles blocks the adaptive treatment tolerance of cancer cells

Abstract

The adaptive treatment tolerance (ATT) of cancer cells is the main encumbrance to cancer chemotherapy. A potential solution to this problem is to treat cancer cells with multiple drugs using nanoparticles (NPs).In this study, we tested the co-administration of curcumin (Cur) and doxorubicin (Dox) to MCF-7 resistant breast cancer cells to block the ATTand elicit efficient cell killing. Drugs were co-administered to cells both sequentially and simultaneously. Sequential drug co-administration was carried out by pre-treating the cells with albumin nanoparticles (ANPs) loaded with Cur (Cur@ANPs) followed by treatment with Dox-loaded ANPs (Dox@ANPs). Simultaneous drug co-administration was carried out by treating the cells with ANPs loaded with both the drugs (Cur/Dox@ANPs). We found that the simultaneous drug co-administration led to a greater intra-cellular accumulation of Dox and cell killing with respect to the sequential drug co-administration. However, the simultaneous drug co-administration led to a lower intracellular accumulation of Cur with respect to the sequential drug co-administration. We showed that this result was due to the aggregation and entrapment of Cur in the lysosomes as soon as it was released from Cur@ANPs, a phenomenon called lysosomotropism. In contrast, the simultaneous release of Dox and Cur from Cur/Dox@ANPs into the lysosomes led to lysosomal pH elevation, which, in turn, avoided Cur aggregation, led to lysosome swelling and drug release in the cytosol, and finally provoked efficient cell killing. Our study shed the light on the molecular processes driving the therapeutic effects of anti-cancer drugs co-administered to cancer cells in different manners. Biophysics ReportsRESULTS AND DISCUSSION Preparation and characterization of albumin nanoparticles loaded with Cur and/or Dox Bovine serum albumin (BSA) nanoparticles (ANPs) loaded with Cur (Cur@ANPs), Dox (Dox@ANPs), or both RESEARCH ARTICLE S. M. Motevalli et al.

Natural and engineered bacterial outer membrane vesicles

“…There are probably 18.1 million new cancer cases and 9.6 million cancer deaths worldwide in 2018 (Bray et al 2018). No time to lose in the fight against cancer (Motevalli et al 2019;Sun et al 2018). Previous lines of research have reported that bacteria such as Bifidobacterium bifidum and E. coli have ability to target tumor, proliferate in specific tumor cells, and trigger effective antitumor through specific immune factormediated immune response (Kim et al 2015a, b;Pawelek et al 2003).…”

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

“…This proved that the hydrogel and the polymer do not have any biocompatibility-related issues and that the empty material does not possess any therapeutic property. Furthermore, the free RESV/DOX (54.97 ± 3.80%)-treated group showed larger necrotic area than the single drug-loaded hydrogel-based treated groups (Na-DOX-hyd-RESV and Na-DOC-hyd+G4.5-DOX), which could mainly be due to systemic toxicity of the freely diffused DOX in the area [ 61 ]. Based on the results of the in vivo model mice study, we concluded that the highest tumor growth inhibition was observed in mice treated with Na-DOX-RESV+G4.5-DOX, as this formulation offers synergistic antitumor effect due to sequential, controlled, and sustained release of the drugs at the tumor sites.…”

Natural Ingredient-Based Polymeric Nanoparticles for Cancer Treatment

“…Curcumin showed slower release as compared to doxorubicin, presumably because it is more hydrophobic than doxorubicin. Therefore, curcumin could interact with the domains of albumin more strongly [81,82]. Experimental results exhibited that curcumin and doxorubicin coencapsulated in albumin nanoparticles were able to decrease the ATT effect.…”

“…On the contrary, if curcumin and doxorubicin were delivered on separate nanoparticles, curcumin would aggregate and be entrapped by lysosomes, making it unable to block P-glycoprotein in the cytosol [83]. As a result, any doxorubicin taken up by the cancer cells would be moved out [81]. Another DDS based on bovine serum albumin nanoparticles for codelivery of doxorubicin and cyclopamine was developed by Lu et al Similar to curcumin, cyclopamine can increase doxorubicin accumulation by inhibiting P-glycoprotein expression [84,85].…”