Recent advances in arsenic trioxide encapsulated nanoparticles as drug delivery agents to solid cancers

Since arsenic trioxide (ATO) was first approved as the front line therapy for acute promyelocytic leukemia (APL) 25 years ago, its anti-cancer properties for various malignancies have been under intense investigation. However, the clinical successes of ATO in treating hematological cancers have not been translated to solid cancers. This is due to arsenic’s rapid clearance by the body’s immune system before reaching the tumor site. Several attempts have henceforth been made to increase its bioavailability toward solid cancers without increasing its dosage albeit without much success. This review summarizes the past and current utilization of ATO in the medical field with primary focus on the implementation of nanotechnology for ATO delivery to solid cancer cells. Different approaches that have been employed to increase arsenic’s efficacy, specificity and bioavailability to solid cancer cells were evaluated and compared. The potential of combining different approaches or tailoring delivery vehicles to target specific types of solid cancers according to individual cancer characteristics and arsenic chemistry was proposed and discussed

Anti-cancer natural products isolated from chinese medicinal herbs

In recent years, a number of natural products isolated from Chinese herbs have been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, retard metastasis and enhance chemotherapy, exhibiting anti-cancer potential both in vitro and in vivo. This article summarizes recent advances in in vitro and in vivo research on the anti-cancer effects and related mechanisms of some promising natural products. These natural products are also reviewed for their therapeutic potentials, including flavonoids (gambogic acid, curcumin, wogonin and silibinin), alkaloids (berberine), terpenes (artemisinin, β-elemene, oridonin, triptolide, and ursolic acid), quinones (shikonin and emodin) and saponins (ginsenoside Rg3), which are isolated from Chinese medicinal herbs. In particular, the discovery of the new use of artemisinin derivatives as excellent anti-cancer drugs is also reviewed

Multimodal Decorations of Mesoporous Silica Nanoparticles for Improved Cancer Therapy

The presence of leaky vasculature and the lack of lymphatic drainage of small structures by the solid tumors formulate nanoparticles as promising delivery vehicles in cancer therapy. In particular, among various nanoparticles, the mesoporous silica nanoparticles (MSN) exhibit numerous outstanding features, including mechanical thermal and chemical stability, huge surface area and ordered porous interior to store different anti-cancer therapeutics with high loading capacity and tunable release mechanisms. Furthermore, one can easily decorate the surface of MSN by attaching ligands for active targeting specifically to the cancer region exploiting overexpressed receptors. The controlled release of drugs to the disease site without any leakage to healthy tissues can be achieved by employing environment responsive gatekeepers for the end-capping of MSN. To achieve precise cancer chemotherapy, the most desired delivery system should possess high loading efficiency, site-specificity and capacity of controlled release. In this review we will focus on multimodal decorations of MSN, which is the most demanding ongoing approach related to MSN application in cancer therapy. Herein, we will report about the recently tried efforts for multimodal modifications of MSN, exploiting both the active targeting and stimuli responsive behavior simultaneously, along with individual targeted delivery and stimuli responsive cancer therapy using MSN

Filomicelles Deliver A Chemo-Differentiative Therapy To Durably Control Carcinoma Cell Fate

Current chemotherapy causes a host of side effects and better delivery of drugs to tumors is required to reduce this. Nanocarriers have been proven to not only deliver better to tumors but also solubilize more drugs in the core, with flexible ‘filomicelles’ being particularly effective. They are still open to improvements and one obvious way is to increase drug loading and hence drug dosage delivered to tumors. In the first part, the core of filomicelles was modified by the integration of aromatic groups into the hydrophobic block of a degradable di-block copolymer with the aim of improving delivery of aromatic drugs. Formed by self-assembly of amphiphilic di-block copolymer PEG-PBCL, flexible worm-like micelles with an aromatic core loaded more Paclitaxel than analogous aliphatic systems. The death of cancer cells and ploidy in surviving cells were higher followed by tumor shrinkage in vivo. When cancer cells are treated with single drugs alone during chemotherapy, development of drug resistance has been commonly noted, eventually leading to relapse. Retinoic acid (RA) induces differentiation and proliferation arrest in many cell types. With carcinoma lines, we find dual drug treatment with RA and Paclitaxel increases ploidy and cell death beyond those achieved by either drug single-handedly, with effects being durable. A month after treatment, relapse rates are low for RA-TAX treated cells (15%), compared to almost all (92%) for cells treated with Paclitaxel alone. Reduction in levels of key cell cycle factor Cyclin-D1 and proliferation marker Ki-67 help clarify the basis for this synergy. These effects are greatly enhanced by loading the drugs into filomicelles. Co-loading the drugs into filomicelles lead to a more potent system compared to separate loading, with no loss in the integration efficiency of drugs. Notably, relapse rates were ~2% three months after treatment, highlighting the improvement offered by filomicelles. The combination retains its potency across multiple cell lines despite their varying responsiveness to RA alone. Drug loaded filomicelles are able to shrink subcutaneous lung and liver tumors in vivo. Tumor shrinkage was also observed with orthotopic liver tumors, leading to a survival benefit. These results highlight the irreversible synergy of killing cancerous cells while driving differentiation

Paradox Role of Oxidative Stress in Cancer

Reactive oxygen species (ROS) are produced by healthy cells and are maintained at physiological levels by antioxidant systems. However, when ROS increase in number, a condition of oxidative stress occurs, leading to many human diseases, including cancer. The relationship between oxidative stress and cancer is complex since ROS play a double-edged role in cancer development and under therapy response. This paradox represents a great challenge for researchers and needs to be investigated. The articles collected in this Special Issue can help to clarify the role of ROS modulation in cancer prevention and treatment, and to dissect the molecular mechanisms underlying its paradoxical role in order to counteract carcinogenesis or enhance sensitivity to anticancer therapy