<p>Carrier-Free, Dual-Functional Nanorods Via Self-Assembly Of Pure Drug Molecules For Synergistic Chemo-Photodynamic Therapy</p>

Abstract

BackgroundThe combination of chemo-photodynamic therapy based on nano-technology has emerged as a preferable and promising measure for synergetic antitumor therapy.PurposeThe aim of this study was expected to overcome most of the safety concerns from nano-carriers and improve the chemo-photodynamic synergistic antitumor efficacy.MethodsHerein, we reported a facile and effective approach based on the self-assembly of chemotherapeutic agent 10-hydroxycamptothecin (HCPT) and photosensitizer chlorin e6 (Ce6) for preparing stably dual-functional nanorods (NRs).ResultsThe chemical thermodynamic parameters obtained from isothermal titration calorimeter (ITC) and the microcosmic configuration snapshots acquired by molecular dynamics (MD) simulations verified that HCPT and Ce6 molecules tended to assemble with each other through various intermolecular forces. The as-prepared HCPT/Ce6 NRs possessed a relatively uniform size of around 165 nm and zeta potential of about −29 mV, together with good stability in aqueous solution and freeze-dried state. In addition, both the extra- and intracellular reactive oxygen species (ROS) generation capacity of the NRs under laser irradiation was significantly enhanced compared with Ce6 injections. Moreover, the dual-functional HCPT/Ce6 NRs exhibited a substantial in vitro/in vivo synergistic antitumor efficacy under laser irradiation due to the integration of the two therapeutic modalities into one drug delivery system. Besides, no obvious hepatic or renal toxicity was observed in the NRs treatment groups.ConclusionTaken together, HCPT/Ce6 NRs demonstrated a powerful efficacy in chemo-photodynamic therapy for breast cancer. Therefore, the carrier-free dual-functional NRs prepared in a facile and effective strategy might give inspiration for the development of combined antitumor therapy.

Bioactive Natural Small Molecule-Tuned Coassembly of Photosensitive Drugs for Highly Efficient Synergistic and Enhanced Type I Photochemotherapy

“…Unexpectedly, under rigorous, same conditions, we found that all formulations could form a uniform spherical nanostructure even if without sonication (0 min) (Figure S8), suggesting that a stronger intermolecular interaction exists between these two species to promote the coassembly easily. This coassembly of BC with Ce6 may be spontaneous with a negative Gibbs free energy change (Δ G °) similar to HCPT/Ce6 coassemblies . As the ultrasonic time extended from 0 to 8 min, BC-Ce6 NPs exhibit obviously decreased size (Figure S9), and this dimensional change after continuous ultrasound also leads to the enhanced π–π stacking in the molecular level (Figure S10).…”

“…This coassembly of BC with Ce6 may be spontaneous with a negative Gibbs free energy change (ΔG°) similar to HCPT/ Ce6 coassemblies. 28 As the ultrasonic time extended from 0 to 8 min, BC-Ce6 NPs exhibit obviously decreased size (Figure S9), and this dimensional change after continuous ultrasound also leads to the enhanced π−π stacking in the molecular level (Figure S10). Generally, the intermolecular interactions in the supramolecular nanostructure are basically noncovalent interactions, for instance, π−π stacking, hydrogen bonding, and van der Waals forces.…”

Carrier-Free Triterpene Prodrugs with Glutathione Response and Biosafety for Synergistically Enhanced Photochemotherapy

“…Additionally, because of these associative noncovalent interactions, BA-S-S and Ce6 could be assembled easily even without sonication (Figure S5), implying that this coassembly may be spontaneously similar to HCPT/Ce6 coassemblies. 37 To further visualize the coassembly and reveal the underlying possible molecular mechanism why free BA-S-S could form long lamella-like self-assemblies, while BA-S-S/Ce6 coassemblies form spherical nanoparticles, we performed a molecular dynamics (MD) simulation of a simplified model with 12 density functional theory (DFT)-optimized BA-S-S molecules and additional 3 Ce6 molecules in a water box. Initially, we investigated the possible interaction/binding of BA-S-S self-assemblies (Figure 2A).…”

“…Collectively, we reasonably believe that the successful coassembly of BA-S-S with Ce6 molecules may be primarily attributed to the π–π stacking and hydrophobic interactions. Additionally, because of these associative noncovalent interactions, BA-S-S and Ce6 could be assembled easily even without sonication (Figure S5), implying that this coassembly may be spontaneously similar to HCPT/Ce6 coassemblies …”

Albumin-encapsulated Nanoparticles of Naproxen Platinum(IV) Complexes with Inflammation Inhibitory Competence Displaying Effective Antitumor Activities in vitro and in vivo

“…Moreover, taking advantage of the enhanced permeability and retention (EPR) effect in tumor tissues, nanoparticles (NPs) facilitate drug targeting to tumor tissues, and further influence their activities and toxic properties. 4 , 5 The investigation on nano-DDS of chemotherapeutics has been a hot topic in cancer treatments.…”