Targeted Delivery to Tumors: Multidirectional Strategies to Improve Treatment Efficiency

Abstract

Malignant tumors are characterized by structural and molecular peculiarities providing a possibility to directionally deliver antitumor drugs with minimal impact on healthy tissues and reduced side effects. Newly formed blood vessels in malignant lesions exhibit chaotic growth, disordered structure, irregular shape and diameter, protrusions, and blind ends, resulting in immature vasculature; the newly formed lymphatic vessels also have aberrant structure. Structural features of the tumor vasculature determine relatively easy penetration of large molecules as well as nanometer-sized particles through a blood–tissue barrier and their accumulation in a tumor tissue. Also, malignant cells have altered molecular profile due to significant changes in tumor cell metabolism at every level from the genome to metabolome. Recently, the tumor interaction with cells of immune system becomes the focus of particular attention, that among others findings resulted in extensive study of cells with preferential tropism to tumor. In this review we summarize the information on the diversity of currently existing approaches to targeted drug delivery to tumor, including (i) passive targeting based on the specific features of tumor vasculature, (ii) active targeting which implies a specific binding of the antitumor agent with its molecular target, and (iii) cell-mediated tumor targeting.

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

“…For example, EVs derived from APCs can express membranebound complement regulators CD55 and CD59 to enhance the stability in vivo (Clayton et al, 2003). EVs could stay in circulation for a quite long time even when exposed to harsh inflammatory environment (Armstrong et al, 2017;Kutova et al, 2019). In addition, a CD47-mediated protection of EVs from mononuclear phagocytic systems expressed 'don't eat me' signal which increases the time of EV in circulation (Kamerkar et al, 2017).…”

Trimeric Small Interfering RNAs and Their Cholesterol-Containing Conjugates Exhibit Improved Accumulation in Tumors, but Dramatically Reduced Silencing Activity

“…Since the properties of vasculature are one of the most important factors determining the efficiency of accumulation in a particular organ, optimization of the conjugate size is required for each target organ, while it is not obvious that this approach will have an advantage for the number of organs. In the case of the conjugates described in this article, the enhanced accumulation of conjugates is apparently provided by the effect of enhanced permeability and retention in the tumor [16], which opens up the possibility of concentrating efforts on their design for oncology purposes.…”

“…The accumulation of siRNA preparations in organs is mainly determined by the duration of their presence in the bloodstream and the characteristic of organ vasculature [15]. An important role in the accumulation of therapeutic nucleic acids in tumors is played by the effect of enhanced permeability and retention (EPR), which is caused by higher vascular permeability of the tumor and deterioration of lymphatic drainage [16]. The data obtained showed that an increase in the molecular weight of the conjugate does not prevent its exit from the vessels and accumulation in the ornaments, and in the case of a tumor, provides a more effective retention in the Quantitative data were obtained by stem-loop PCR using calibration curves with known concentrations of the studied drugs added to samples of the corresponding organs of untreated mice.…”

Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

“…NCs aim to increase efficiency of drug delivery to tumor sites, improve stability and solubility of drugs and in some cases improve therapeutic efficacy of the drug. There are NCs that “passively” target tumor cites, meaning that they passively accumulate in tumor tissue due to the higher permeability of blood vessels in tumor site (“enhanced permeability and retention (EPR) effect”) . Another type of NCs functionalized with affinity ligands specific for cancer cells or tumor environment are designed to “actively” target tumors …”