Abstract
Dual functional drug carrier has been a modern strategy in cancer therapy because it is a platform to elicit additive and synergistic effects through combination therapy. Photo-activated external stimuli such as reactive oxygen species (ROS) also ensure adequate drug delivery in a precise temporal and spatial manner. However, current ROS-responsive drug delivery systems usually require tedious synthetic procedures. A facile one-pot approach has been reported herein, to obtain self-assembled polymeric nanocarriers (NCs) for simultaneous paclitaxel (PTX)- and Rose Bengal (RB)-loading to achieve combined chemo-photodynamic therapy and controlled drug release in responsive to a light-induced ROS stimulus. To encapsulate these hydrophobic and hydrophilic drugs, chitosan (CTS), branched polyethylenimine (bPEI) and polyvinyl alcohol (PVA) were selected and fabricated into nanoblended matrices through an oil-in-water emulsion method. The amphiphilic properties of CTS permit simultaneous entrapment of PTX and RB, while the encapsulation efficiency of RB was further improved by increasing the amount of short-chain bPEI. During the one-step assembly process, bovine serum albumin (BSA) was also added to condense the cationic tripolymer mixtures into more stable nanocarriers (BNCs). Hyaluronic acid (HA) was subsequently grafted onto the surface of BNCs through electrostatic interaction, leading to the formation of HA-BSA/CTS/PVA/bPEI-blended nanocarriers (HBNCs) to achieve an efficient prostate-cancer-cell uptake. Importantly, in response to external light irradiation, HBNCs become destabilized owing to the RB-mediated photodynamic action. It allows an on-demand dual-payload release to evoke a simultaneous photodynamic and chemo treatment for cancer cell eradication. Thus, HBNCs present a new promising approach that exhibits a specific vulnerability to RB-induced photosensitization. The consequent dual-cargo release is also expected to successfully combat cancer through a synergistic anti-tumor effect.
Highlights
As an extremely complex disease, cancer causes a serious threat to human health
The size distributions of the resulting NCs, HA-CTS/PVA/bPEI-Blended Nanocarriers (HNCs), Blended Nanocarriers (BNCs), and HA-BSA/CTS/PVA/bPEI-blended nanocarriers (HBNCs) were characterized by dynamic light scattering (DLS) analysis
Both of the BNCs and HBNCs presented the greatest quantity in the precipitate, indicating that nanoparticles made with bovine serum albumin (BSA) attain the highest production yield
Summary
As an extremely complex disease, cancer causes a serious threat to human health. It involves numerous tempo-spatial changes in cell physiology along with complex signaling pathways, enabling tumor cells to evade programmed cell death, making the treatment extremely challenging (Hanahan and Weinberg, 2000, 2011). The loading efficiency of RB into NCs, HNCs, BNCs, and HBNCs were determined by UV-Vis absorption spectrum measurement (Cary 100, Varian, Palo Alto, CA, USA), respectively. Cells were incubated with RB/PTX-loaded HBNCs in complete culture medium for 6 h and washed twice in DPBS.
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