Combating Cancer with Novel Technologies

The nanostructured drugs for cancer treatment that have so far reached the oncology market largely rely on passive targeting (p.e.: Abraxane, Doxil, Daunoxome, Oncaspar, DepoCyt), meaning that they are not empowered by specific mechanisms to recognize specific cell types or tissues. Preferential but still passive accumulation into tumor tissues is thus favored; in addition the increase in circulation time is promoted by the nanoscale size of the drug-vehicle conjugate contributing to the enhanced permeability and retention effect (EPR) [1]. The amount of drug that reaches target cells is supposed to remain low rather insufficient to ensure the desired therapeutic response. Most of such conventional chemotherapeutic drugs (e.g., 5-fluorouracil) exert their antitumor effect by interfering with nucleic acid synthesis and inhibiting tumor cell proliferation. When the level of DNA damage in exposed cells exceeds their repair capacity, the induction for cell death follows. The low molecular weight of anticancer drug allows their free diffusion through the body, as a result they also reach normal tissues. Their greatest effect occurs, however, in highly proliferative normal cells (i.e., bone marrow and intestinal tract), often causing dose-limiting myelosuppression and gastrointestinal toxicities. The conjunction of this narrow therapeutic index and the considerable inter-individual differences in distribution, metabolism and excretion of these cytotoxic agents in humans, result in an increased risk of toxicity and also sub-therapeutic dosing in the individual patient [2]. This limitation as a problem may soon change since many actively targeted nanoparticles for drug delivery are being evaluated in clinical assays. Among them, polymer-lipid hybrid nanoconstructs, liposomes, reverse micelles and core shell nanoparticles are our present research area [3]. The polymeric NPs are colloidal particles, which are self-assembled in case of amphiphilic block copolymers when exposed to an aqueous media. They offer several benefits such as a higher drug pay load, prolonged blood circulation, and controlled release profiles. In polymeric NPs, the hydrophobic cytotoxic drugs can be easily encapsulated into the hydrophobic core. The outer exposed hydrophilic part provided the stable dispersion by imparting a steric stabilization that ultimately enhanced its blood residence time following intravenous injection. Poly lactic-coglycolic acid (PLGA) is commonly exploited for drug delivery and in the biomedical field owing to its excellent biocompatible, biodegradable nature and well-established safety in clinic applications. However, the block copolymer of PLGA with poly ethylene glycol (PEG) as mPEG-PLGA offers an attractive option owing to PEGylated polymeric NPs diminishing the systemic clearance as compared to non-PEGylated particles. Further with similar size they are successfully employed for passive targeting. They accumulated the tumor site through enhanced permeability and retention (EPR) effects. The continual advancements in drug delivery science and biotechnology together offers various targeting options that specifically identify and bind the receptors that are overexpressed on angiogenic vessels within solid tumors and also on tumor cells [3].