Alteration of Tumor Microenvironment for Improved Delivery and Intratumor Distribution of Nanocarriers

Abstract

Nanocarrier-based cancer chemotherapeutics are thought to increase therapeutic efficiency and reduce the side effects of associated chemotherapeutic agents by altering the agents' pharmacokinetics and tissue distribution following intravenous administration. In spite of these favorable properties, nanocarrier-based cancer chemotherapeutics are not always effective because of their heterogeneous intratumoral localization. Homogeneous distribution of nanocarriers in a tumor would improve the efficacy of nanocarrier-based cancer chemotherapeutics. In this article, we describe and discuss some trials that attempt to manipulate the barriers in the tumor microenvironment that hinder extravasation through the tumor vasculature and penetration of nanocarriers in solid tumors. Alterations of the tumor microenvironment that relate directly to the intratumoral distribution of nanocarriers may be potential strategies to improve the delivery of nanocarrierbased cancer chemotherapeutics.

Drug delivery system based on dendritic nanoparticles for enhancement of intravesical instillation

“…Some studies have pointed out that nanoparticles ,50 nm may penetrate into deeper tissue 34,35 because larger particles may have poor delivery to less leaky sites in highly heterogeneous tumor tissues 36 and narrow spacing between tumor cells. 37,38 The diameter of a poly (amido amine) generation 5.0 (PAMAM G5) dendrimer used in our study is about 5.4 nm. Even after surface modification with PEG and loading with DOX, the mean diameter of the complex is only about 13 nm (Figure 2), which is far smaller than most reported nanoparticles for intravesical instillation (usually .100 nm).…”

Rational Approaches for Combination Therapy Strategies Targeting the MAP Kinase Pathway in Solid Tumors

“…The unconfirmed ORR was 60% (9 PR, 2 SD, and 3 PD). Incorporation of nanoparticle systems may overcome toxicity associated with horizontal inhibition by targeting drug delivery to the tumor site at therapeutic levels while sparing the rest of the body from off-target toxicities (98,99). Polymeric micelles and liposome nanoparticles have been found to preferentially accumulate in solid tumors.…”

“…Polymeric micelles and liposome nanoparticles have been found to preferentially accumulate in solid tumors. This phenomenon, termed the enhanced permeability and retention effect, is thought to be due to the abnormal tumor microenvironment, and researchers are looking for ways to further manipulate this effect to increase drug delivery (99). One study evaluating nanoparticle-mediated delivery of MEK inhibitor PD98059 in a melanoma mouse model showed significant tumor inhibition over vehicle (100).…”

Superparamagnetic reconstituted high-density lipoprotein nanocarriers for magnetically guided drug delivery

“…[6][7][8][9] These include solubility, bioavailability, pharmacokinetics and biological barriers such as tumor microenvironment, hypoxic core and extracellular tumor pH, interstitial fluid pressure and many other factors. [9][10][11][12][13][14][15] Nanotechnology has been invoked as a means of overcoming several of these difficulties. 16 More specifically, cancer chemotherapy is frequently associated with short-and long-term side effects, [17][18][19][20] affecting the quality of life of cancer survivors.…”