Co-Delivery of Cisplatin Prodrug and Chlorin e6 by Mesoporous Silica Nanoparticles for Chemo-Photodynamic Combination Therapy to Combat Drug Resistance

Abstract

Combination therapy shows great promise in circumventing cisplatin resistance. We report herein the development of a novel nanoscale drug delivery system (nDDS) based nanotherapeutic that combines chemotherapy and photodynamic therapy (PDT) into one single platform to achieve synergistic anticancer capacity to conquer cisplatin resistance. Mesoporous silica nanoparticle (MSNs) was used as the drug delivery vector to conjugate cisplatin prodrug and to load photosensitizer chlorin e6 (Ce6) to afford the dual drug loaded delivery system MSNs/Ce6/Pt. The hybrid nanoparticles have an average diameter of about 100 nm and slightly positive surface charge of about 18.2 mV. The MSNs/Ce6/Pt nanoparticles can be efficiently internalized by cells through endocytosis, thereby achieving much higher cellular Pt uptake than cisplatin in cisplatin-resistant A549R lung cancer cells. After 660 nm light irradiation (10 mW/cm(2)), the cellular reactive oxygen species (ROS) level in MSNs/Ce6/Pt treated cells was elevated dramatically. As a result of these properties, MSNs/Ce6/Pt exhibited very potent anticancer activity against A549R cells, giving a half-maximal inhibitory concentration (IC50) value for the combination therapy of 0.53 μM, much lower than that of cisplatin (25.1 μM). This study suggests the great potential of nDDS-based nanotherapeutic for combined chemo-photodynamic therapy to circumvent cisplatin resistance.

Nanoformulations for combination or cascade anticancer therapy

“…Therefore, “PDT+chemotherapy” has been hypothesized and shown to be a powerful combination strategy in destroying cancer tissues. So far, versatile materials have been applied to encapsulate chemotherapy with photosensitizers, such as synthetic polymers [231], lipids, inorganic materials [136] or biomacromolecule scaffolds. However, due to the particular structure of photosensitizers (i.e.…”

Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance

“…It is propitious for S-D1@L-D2 NPs to transport through blood vessels and retain in circulation for long periods, as well as internalize by means of endocytosis. 25,37,38 Its inner smaller…”

Carrier-free, self-assembled pure drug nanorods composed of 10-hydroxycamptothecin and chlorin e6 for combinatorial chemo-photodynamic antitumor therapy in vivo

“…However, the intrinsic limitations of the conventional cancer therapies (for example, poor water solubility of some drugs, lack of targeting ability, sever side effect, drug resistance) are always huge obstacles to satisfactory outcomes of cancer treatment. 3–7 Recent years, nanomedicine has emerged as an innovative and promising strategy for more effective and safer cancer treatment. 8–11 Tremendous attention has been paid to develop various kinds of nanoscale drug delivery systems (nDDS), such as liposomes, 12–15 dendrimers, 16–18 micelles, 19–23 inorganic nanomaterials, 24–30 and so on.…”