The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors

Abstract

Nanomaterial (NM) delivery to solid tumors has been the focus of intense research for over a decade. Classically, scientists have tried to improve NM delivery by employing passive or active targeting strategies, making use of the so-called enhanced permeability and retention (EPR) effect. This phenomenon is made possible due to the leaky tumor vasculature through which NMs can leave the bloodstream, traverse through the gaps in the endothelial lining of the vessels, and enter the tumor. Recent studies have shown that despite many efforts to employ the EPR effect, this process remains very poor. Furthermore, the role of the EPR effect has been called into question, where it has been suggested that NMs enter the tumor via active mechanisms and not through the endothelial gaps. In this review, we provide a short overview of the EPR and mechanisms to enhance it, after which we focus on alternative delivery strategies that do not solely rely on EPR in itself but can offer interesting pharmacological, physical, and biological solutions for enhanced delivery. We discuss the strengths and shortcomings of these different strategies and suggest combinatorial approaches as the ideal path forward.

Stereocomplex Polylactide for Drug Delivery and Biomedical Applications: A Review

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Nanocarriers Used in Drug Delivery to Enhance Immune System in Cancer Therapy

“…Among the nanocarriers that are being developed for the diagnosis and treatment of cancer are inorganic nanoparticles, which may consist of iron oxide, silica, gold, and graphene, among other compounds [ 46 ]. There is greater difficulty in translating these types of nanomaterials (NMs) to clinical application, due to their lower biocompatibility and the lack of understanding of possible complications caused by their deposition in different organs, such as greater stability, less hydrophobicity, and non-microbial storage [ 47 , 48 ].…”

Pyroelectric Catalysis-Based “Nano-Lymphatic” Reduces Tumor Interstitial Pressure for Enhanced Penetration and Hydrodynamic Therapy

“…Nowadays, drug delivery has become one of the most controversial issues, which is also the top concern of all anticancer therapies, with the rapid development of nanomedicines [1][2][3][4][5] . The major obstacle in achieving better delivery e ciency is the abnormally high tumor interstitial pressure (TIP) [6][7][8][9] .…”

“…However, the interstitial pressure in the tumor is as high as 30~130 mmHg due to the retention of interstitial uid caused by de cient lymph-vessel and lymphatic re ux, as well as dense extracellular matrix (ECM) [13][14][15] . The much smaller net outward pressure or even net inward pressure seriously limits the normal ow from vessels into the tumor 3 , which leads to unsatisfactory delivery e ciency of therapeutic agents. Among the mounting works on drug delivery, most efforts focus on reducing tumor interstitial solid pressure (TISP) caused by dense ECM, proteins, and broblasts via enzymolysis, which left the mass deposition of interstitial uid unsolved [16][17][18] .…”