Dual Targeted Delivery of Liposomal Hybrid Gold Nano-Assembly for Enhanced Photothermal Therapy against Lung Carcinomas.

The delivery and accumulation of therapeutic drugs into cancer cells without affecting healthy cells are a major challenge for antitumor therapy. Here, we report the synthesis of a liposomal hybrid gold nano-assembly with enhanced photothermal activity for lung cancer treatment. The core components of the nano-assembly include gold nanorods coated with a mesoporous silica shell that offers an excellent drug-loading surface for encapsulation of doxorubicin. To enhance the photothermal capacity of nano-assembly, IR 780 dye was loaded inside a thermo-sensitive liposome, and then, the core nano-assembly was wrapped within the liposome, and GE-11 peptide and folic acid were conjugated onto the surface of the liposome to give the final nano-assembly [(GM@Dox) LI]-PF. The dual targeting approach of [(GM@Dox) LI]-PF leads to enhanced cellular uptake and improves the accumulation of nano-assemblies in cancer cells that overexpress the epidermal growth factor receptor and folate. The exposure of near-infrared laser irradiation can trigger photothermal-induced structural disruption of the nano-assembly, which allows for the precise and controllable release of Dox at targeted sites. Additionally, chemo-photothermal therapy was shown to be 11 times more effective in cancer cell treatment when compared to Dox alone. Our systematic study suggests that the nano-assemblies facilitate the cancer cells undergoing apoptosis via an intrinsic mitochondrial pathway that can be directly triggered by the chemo-photothermal treatment. This study offers an appealing candidate that holds great promise for synergistic cancer treatment.

Fabrication of a Dual-Targeted Liposome-Coated Mesoporous Silica Core-Shell Nanoassembly for Targeted Cancer Therapy.

Nanoparticles have been suggested as drug-delivery systems for chemotherapeutic drugs to allow for controlled drug release profiles and selectivity to target cancer cells. In addition, nanoparticles can be used for the in situ generation and amplification of reactive oxygen species (ROS), which have been shown to be a promising strategy for cancer treatment. Thus, a targeted nanoscale drug-delivery platform could be used to synergistically improve cancer treatment by the action of chemotherapeutic drugs and ROS generation. Herein, we propose a promising chemotherapy strategy where the drug-loaded nanoparticles generate high doses of ROS together with the loaded ROS-generating chemotherapeutic drugs, which can damage the mitochondria and activate cell death, potentiating the therapeutic outcome in cancer therapy. In the present study, we have developed a dual-targeted drug-delivery nanoassembly consisting of a mesoporous silica core loaded with the chemotherapeutic, ROS-generating drug, paclitaxel (Px), and coated with a liposome layer for controlled drug release. Two different lung cancer-targeting ligands, folic acid and peptide GE11, were used to target the overexpressed nonsmall lung cancer receptors to create the final nanoassembly (MSN@Px) L-GF. Upon endocytosis by the cancer cells, the liposome layer was degraded by the intracellular lipases, and the drug was rapidly released at a rate of 65% within the first 20 h. In vitro studies confirmed that this nanoassembly was 8-fold more effective in cancer therapy compared to the free drug Px.

Targeted Delivery of Antibiotic Therapy to Inhibit Pseudomonas aeruginosa Using Lipid-Coated Mesoporous Silica Core-Shell Nanoassembly.

Pseudomonas aeruginosa (PA) is an opportunistic pathogen, which causes serious lung infections in immunocompromised patients. Traditional oral intake of large quantities of small-molecule antibiotics to treat bacterial infections leads to off-target toxicity and development of drug-resistant species. Improved delivery systems of antibiotics to the targeted site of bacterial infections would help reduce the need for a high intake of antibiotics. Colistin (Col), an antibacterial peptide, is considered the last resort treatment for multidrug resistant (MDR)-PA. To approach the problem of development of antibacterial resistance and off-target toxicity due to the use of excessive amounts of antibiotics, we have designed a targeted drug delivery nanoassembly, which delivers antibiotics to extracellular and intracellular bacteria. The nanoassembly is composed of (1) drug (Col)-loaded mesoporous silica (MSN) core (Col@MSN), (2) liposomal shell (Col@MSN@LL), and (3) PA-targeting LL-37 peptide (Col@MSN@LL-(LL-37)). The liposomal shell prevents premature drug release before the nanoassembly approaches the targeted bacteria. The liposome bilayer degrades upon excreted lipase present in the local environment of PA, releasing encapsulated Col. There is a significant increase in Col release (∼90% release within 40 h) in the presence of bacteria compared to the absence of bacteria (only ∼75% release after 80 h). A 6.7-fold increase in the antimicrobial efficacy of Col encapsulated in Col@MSN@LL-(LL-37) was seen compared to free Col. All studies were done using a clinical strain of PA14. Col@MSN@LL-(LL-37) successfully targets and inhibits intracellular PA14 within the lung epithelial cells. Only 7% PA14 viability is seen after treating the lung epithelial cells with Col@MSN@LL-(LL-37). No significant cytotoxicity was observed with Col@MSN@LL-(LL-37). Therefore, this discussed lipid-coated targeted nanoassembly can be considered as a successful antibiotic delivery platform.