Format

Send to

Choose Destination
J Control Release. 2015 Mar 10;201:78-89. doi: 10.1016/j.jconrel.2014.12.018. Epub 2014 Dec 17.

Improving drug delivery to solid tumors: priming the tumor microenvironment.

Author information

1
Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 137-701, Republic of Korea.
2
Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 137-701, Republic of Korea; Department of Medical LifeScience, School of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 137-701, Republic of Korea. Electronic address: hkuh@catholic.ac.kr.

Abstract

Malignant transformation and growth of the tumor mass tend to induce changes in the surrounding microenvironment. Abnormality of the tumor microenvironment provides a driving force leading not only to tumor progression, including invasion and metastasis, but also to acquisition of drug resistance, including pharmacokinetic (drug delivery-related) and pharmacodynamic (sensitivity-related) resistance. Drug delivery systems exploiting the enhanced permeability and retention (EPR) effect and active targeting moieties were expected to be able to cope with delivery-related drug resistance. However, recent evidence supports a considerable barrier role of tumors via various mechanisms, which results in imperfect or inefficient EPR and/or targeting effect. The components of the tumor microenvironment such as abnormal tumor vascular system, deregulated composition of the extracellular matrix, and interstitial hypertension (elevated interstitial fluid pressure) collectively or cooperatively hinder the drug distribution, which is prerequisite to the efficacy of nanoparticles and small-molecule drugs used in cancer medicine. Hence, the abnormal tumor microenvironment has recently been suggested to be a promising target for the improvement of drug delivery to improve therapeutic efficacy. Strategies to modulate the abnormal tumor microenvironment, referred to here as "solid tumor priming" (vascular normalization and/or solid stress alleviation leading to improvement in blood perfusion and convective molecular movement), have shown promising results in the enhancement of drug delivery and anticancer efficacy. These strategies may provide a novel avenue for the development of new chemotherapeutics and combination chemotherapeutic regimens as well as reassessment of previously ineffective agents.

KEYWORDS:

Drug efficacy; Solid stress; Tumor microenvironment; Tumor priming; Tumor stroma; Vascular normalization

PMID:
25526702
DOI:
10.1016/j.jconrel.2014.12.018
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center