Targeted Nanomedicines for Cancer Therapy, From Basics to Clinical Trials

Abstract

Traditional systemic chemotherapy involves the wide distribution of drug molecules in the body, causing toxic side effects in the healthy tissues and limiting the therapeutic dose required at the site of drug action. In order to decrease side effects and increase the drug efficacy, recent research on chemotherapy focuses on drug targeting. Targeted therapy can be achieved by several mechanisms including; 1) using an antibody as a drug that is specific to a disease biomarker, 2) using an antibody (or peptide) as a targeting agent conjugated to the drug molecule, 3) delivering the drug molecules to the target tissue in a nano-carrier with or without the targeting agent attached on its surface. The third approach involves the nanomedicines that can be targeted to diseased tissues by both passive (extravasating at diseased sites due to leaky vasculature) and active (specific interaction of the targeting agent with disease biomarker) targeting mechanisms. In this review we will cover the passively targeted nanomedicines prepared using nano drug carriers. Ideally the carrier particle should be in the right size (1-100nm), stable enough to prevent drug leakage during circulation, and safe not to cause any damage to healthy tissues. Competition for all these properties generated many different types of materials to be used as nanodrug delivery systems. After a brief review of most commonly used drug carriers, we discuss the clinical use of the targeted nanomedicines with regard to their pharmacokinetic and pharmacodynamics properties, and how these properties vary from conventional formulations providing free drugs in the circulation after administration.

Engineering the Interface between Inorganic Nanoparticles and Biological Systems through Ligand Design

“…Small molecule ligands (e.g., folic acid, methotrexate, anisamide, cholic acid, daptomycin, fluorine and sugars) have been utilized extensively for conjugation to various inorganic NPs due to their stability, ease of modification and availability [94][95][96]. To date, several therapeutic and diagnostic approaches using active targeting NPs have entered clinical trials, with several gaining FDA approval [97]. Folic acid (FA) is a frequently used targeting moiety due to overexpression of the folate receptor on cancerous cells and inflamed tissue [98][99][100][101][102][103].…”

Solid Lipid Nanoparticles: An Approach to Improve Oral Drug Delivery

“…Because of these benefits, SLN have been widely studied as transporters of drugs for cancer treatment, so their current uses and prospects are discussed in detail in the following section. It is important to highlight some essential features that must have the carrier to be targeted in cancerous tissue such as its correct size (should be 1-100 nm), adequate stability to avoid drug loss, and enough safety to prevent the damage of healthy tissues (80).…”

“…A disadvantage of all these proposed formulations is that, to the best of our knowledge, no clinical studies have yet been conducted to support their use, though in vitro and in vivo work with animals show promising results that include enhanced intracellular delivery and bioavailability of the encapsulated agents (29,82). In this regard, one characteristic to take advantage of, is the high permeability of blood vessels in cancer tissues, because the size of gaps among them is larger than 100 nm, therefore nanoparticles can pass the damaged tissue and remain there, this is the Enhanced Permeability and Retention effect (80).…”

Theoretical study of encapsulation of diethylstilbestrol drug into the inner surface of BNNT toward designing a new nanocarrier for drug delivery systems

“…Using these carriers, the uptake, distribution, transport, accumulation, and elimination of drugs are modified in such a way that better health conditions and considerable effectiveness were attained. In the cancer therapy process, the targeted drug delivery is utilized to release the drug wherever it needs (cancerous tissue), which can reduce the side effects of the drug [11,12]. Among various carriers applied for this purpose, thanks to the unique properties like chemical stability, oxidation resistivity, high specific surface area, large pore volume, independent electronic characteristics from the diameter of the tube, along with inherent biocompatibility, boron nitride nanotubes (BNNTs) are recognized as potential candidates to be used in various medical fields and especially targeted drug delivery [13][14][15][16].…”

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In this research, the encapsulation and intermolecular non-bonded interactions of an anticancer drug, Diethylstilbestrol (DES), into the inner surfaces of BNNT (8,[8][9][10][11][12] were investigated. All Density Functional Theory (DFT) calculations were performed in a gas phase.

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