Safe Tumor Therapy Research Articles

Simple and Multifunctional Natural Self-Assembled Sterols with Anticancer Activity-Mediated Supramolecular Photosensitizers for Enhanced Antitumor Photodynamic Therapy.

Supramolecular photosensitizers based on nanosized drug delivery or combination therapy have been proposed as a promising strategy for cancer treatment. Herein, we screen and develop a series of multifunctional single-component, carrier-based, natural small-molecule sterols (ergosterol, β-sitosterol, and stigmasterol) that simultaneously possess self-assembly ability, anticancer activity, and better biocompatibility and biodegradability to deliver photosensitizer chlorin e6 (Ce6) for significantly combined and safe antitumor photodynamic therapy. The resultant ergosterol-Ce6 nanodrugs (Ergo-Ce6 NPs) have enhanced reactive oxygen species (ROS) generation by promoting type I photoreactions, while Ce6 mainly exists in the monomer state in assembled Ergo-Ce6 NPs via intermolecular π-π stacking and hydrophobic interactions. In addition, with the improved water solubility and stability and higher intercellular ROS generation, Ergo-Ce6 NPs show remarkably in vitro phototoxicity with approximately 73% and 92% cell inhibition ratios to 4T1 and MCF-7 cancer cells at a rather low dosage of Ce6 (1 μg/mL), respectively. Moreover, the excellent tumor targeting ability of Ergo NPs and prolonged blood circulation ensure a quick tumor accumulation of Ergo-Ce6 NPs, resulting in a significantly enhanced in vivo anticancer efficiency of 86.4%, higher than that of the anticancer ability of Ergo NPs (51.0%) or Ce6 PDT alone (59.5%). Furthermore, the resulting nanodrugs have better biocompatibility and biodegradability and low in vivo toxicity, and all of which ensure a safe tumor therapy. This study provides a promising perspective to develop more natural self-assembled biological small-molecule nanomaterials for the fabrication of novel medicinal photosensitizers for clinical application in the future.

Self-Assembled Peptide-Lanthanide Nanoclusters for Safe Tumor Therapy: Overcoming and Utilizing Biological Barriers to Peptide Drug Delivery.

Developing a sophisticated nanomedicine platform to deliver therapeutics effectively and safely into tumor/cancer cells remains challenging in the field of nanomedicine. In particular, reliable peptide drug delivery systems capable of overcoming biological barriers are still lacking. Here, we developed a simple, rapid, and robust strategy to manufacture nanoclusters of ∼90 nm in diameter that are self-assembled from lanthanide-doped nanoparticles (5 nm), two anticancer peptides with different targets (BIM and PMI), and one cyclic peptide iNGR targeted to cancer cells. The peptide-lanthanide nanoclusters (LDC-PMI-BIM-iNGR) enhanced the resistance of peptide drugs to proteolysis, disassembled in response to reductive conditions that are present in the tumor microenvironment and inhibited cancer cell growth in vitro and in vivo. Notably, LDC-PMI-BIM-iNGR exhibited extremely low systemic toxicity and side effects in vivo. Thus, the peptide-lanthanide nanocluster may serve as an ideal multifunctional platform for safe, targeted, and efficient peptide drug delivery in cancer therapy.

Learning from Clostridium novyi-NT: How to defeat cancer.

Side effects associated with conventional anticancer therapies have prompted the new idea of solid tumor treatment strategy. One of them is using bacteria explored as potential antitumor agents over more than one century. Notably, the ideal therapy is a specifical target to tumors with limited toxicity. Here, we take "Clostridium novyi" for the search keyword in the PubMed from 2000 to 2015 and describe that C. novyi-NT spores act as "Trojan horse" for bacteriolytic therapy. This therapy is based on the fact that the live and attenuated obligate anaerobic bacteria are capable of binary fission selectively in anoxic areas of solid tumors and direct tumoricidal effects. Our succinct review mainly concentrates on the potential mechanisms of combination bacteriolytic therapy, an effective and safe tumor therapy with the help of C. novyi-NT. Importantly, C. novyi-NT spores were shown to induce solid tumor regression and exhibit the property to initiate an immune response. Therefore, C. novyi-NT spores should be an effective and safe tumor therapy.

Salmonella—allies in the fight against cancer

Cancer has become the second ranking cause of death in the industrialized world. Conventional anti-cancer therapies such as surgery, radiotherapy, and chemotherapy are effective in the treatment of solid tumors only to some extent. Furthermore, they are often associated with severe side effects. Use of bacteria as alternative cancer therapeutics has sporadically been followed over more than a century. The potential to target and colonize solid tumors could be shown for many different bacteria in the meantime. Such bacteria are either obligate anaerobic bacteria like Clostridium or Bifidobacterium or facultative anaerobic like Escherichia coli or Salmonella. Here we describe bacterial strains that were successfully applied mostly in animals bearing model tumors, although first clinical trials have been reported as well. Our review mainly concentrates on Salmonella enterica serovar Typhimurium (S. Typhimurium) since these bacteria were studied most intensively thus far. Importantly, S. Typhimurium were shown not only to colonize large established tumors but also exhibit the property to invade and affect metastases. We report on a potential mechanism by which such bacteria can invade solid tumors. Furthermore, we describe several successful attempts in which the bacteria have been used as carriers for recombinant therapeutic molecules that render bacteria more powerful in eradication of the established tumor. Such attempts should be considered starting points on the way to an effective and safe tumor therapy with the help of bacteria.