Rational Design of Nanoparticles with Deep Tumor Penetration for Effective Treatment of Tumor Metastasis

Abstract

The limited penetration of nanoparticles in primary tumors and metastases remains a great challenge for effective treatment of tumor metastasis. This review outlines the current approaches and summarizes the rational design of nanoparticles with deep tumor penetration capacity for anti-metastasis treatment. There are two ways to achieve better tumor penetration; through rational regulation of the physicochemical properties of nanoparticles and through remodeling of the tumor microenvironment, including the tumor vasculature and stromal environment. Moreover, biomimetic strategies that integrate the advantages of nanoparticles and metastasis-homing molecules during cancer cell metastasis are discussed. These efforts have led to promising results in facilitating intratumoral permeation of various nanoparticles to enhance antitumor effects. The considerations and some feasible future directions for deep tumor penetration strategies are proposed to improve tumor metastasis therapies.

Reprogramming Tumor Associated Macrophages toward M1 Phenotypes with Nanomedicine for Anticancer Immunotherapy

“…[ 18,26,27 ] Furthermore, M2‐like TAMs show more phagocytic activity, high expression of scavenging, mannose and galactose lectins. [ 26 ] The abundant and leaky tumor vascular networks, aberrantly upregulated enzymes and highly expressed receptors can be rationally considered to design intelligent nanomedicine to promote their preferential targeting to tumor sites and specific accessibility to TAMs, [ 21,28 ] thereby providing an opportunity to reprogram TAMs into antitumoral M1 phenotype for cancer therapy.…”

“…[ 22,29 ] Moreover, they can be intelligently designed with specific responsiveness to the abnormally expressed enzymes by TAMs to modulate the particle size, morphology, and surface modification, thereby promoting their intratumoral transport in tumor regions. [ 21 ] Likewise, they can be decorated with diverse targeting ligands to facilitate their specific delivery to different cell phenotypes including TAMs in tumor biopsy. [ 30–32 ] We and other groups have revealed that nanoparticles fabricated from polymeric or lipid materials could be preferentially internalized by TAMs in tumor, [ 24 ] thereby providing an essential platform for tumor targeted delivery to reprogram protumoral TAMs toward antitumoral M1 macrophages.…”

“…[ 19,20 ] Nanosized particles can be passively accumulated at tumor sites by exploiting the enhanced permeability and retention effects based on the leakiness of tumor vasculature. [ 21–23 ] Compelling evidence has revealed that rationally designed nanomedicine can effectively permeate across the barriers in tumor mass and preferentially internalized by TAMs, [ 24 ] thereby providing a promising platform for TAMs targeting to facilitate their reprograming toward M1 macrophages for cancer therapy.…”

Real‐Time Imaging Tracking of Engineered Macrophages as Ultrasound‐Triggered Cell Bombs for Cancer Treatment

“…On the other hand, the larger microparticles cannot pass through the endothelial lining, and are easily absorbed by the liver and other immune organs,4,5 which restricts their targeted delivery to diseased tissues. Moreover, the small fraction of the carriers that cross the vasculature are often trapped in the extracellular matrix, and fail to reach the tumor cells due to the high interstitial fluid pressure of solid tumors 6. In addition, some drug delivery systems are potentially toxic and thus ineffective 7.…”

“…Moreover, the small fraction of the carriers that cross the vasculature are often trapped in the extracellular matrix, and fail to reach the tumor cells due to the high interstitial fluid pressure of solid tumors. [6] In addition, some drug delivery systems are potentially toxic and thus ineffective. [7] Therefore, it is essential to develop a novel biomimetic platform with low toxicity and high biocompatibility for targeted drug delivery.…”