Evaluation of uptake and distribution of gold nanoparticles in solid tumors

Abstract

Although nanotherapeutics offer a targeted and potentially less toxic alternative to systemic chemotherapy in cancer treatment, nanotherapeutic transport is typically hindered by abnormal characteristics of tumor tissue. Once nanoparticles targeted to tumor cells arrive in the circulation of tumor vasculature, they must extravasate from irregular vessels and diffuse through the tissue to ideally reach all malignant cells in cytotoxic concentrations. The enhanced permeability and retention effect can be leveraged to promote extravasation of appropriately sized particles from tumor vasculature; however, therapeutic success remains elusive partly due to inadequate intra-tumoral transport promoting heterogeneous nanoparticle uptake and distribution. Irregular tumor vasculature not only hinders particle transport but also sustains hypoxic tissue kregions with quiescent cells, which may be unaffected by cycle-dependent chemotherapeutics released from nanoparticles and thus regrow tumor tissue following nanotherapy. Furthermore, a large proportion of systemically injected nanoparticles may become sequestered by the reticuloendothelial system, resulting in overall diminished efficacy. We review recent work evaluating the uptake and distribution of gold nanoparticles in pre-clinical tumor models, with the goal to help improve nanotherapy outcomes. We also examine the potential role of novel layered gold nanoparticles designed to address some of these critical issues, assessing their uptake and transport in cancerous tissue.

Effects of Nanoparticles on Algae: Adsorption, Distribution, Ecotoxicity and Fate

“…Once the NPs pass through the cell wall, NPs will encounter the second barrier-the plasma membrane. Endocytosis and passive diffusion are considered to be the main pathway for NPs to cross the bilayer lipid membrane [43,44]. In addition, the permeability of the cell wall may change during cell cycling, with the newly synthesized cell wall being more permeable to NPs, thereby increasing the uptake of NPs by algal cells [30,45].…”

111In-labeled trastuzumab-modified gold nanoparticles are cytotoxic in vitro to HER2-positive breast cancer cells and arrest tumor growth in vivo in athymic mice after intratumoral injection

“…AuNP may passively localize in tumors following systemic intravenous (i.v.) injection via the enhanced permeability and retention (EPR) effect due to leaky tumor vasculature and poor lymphatic drainage [2]. AuNP may also be surface modified with monoclonal antibodies (mAbs) or peptide ligands to bind to tumorassociated antigens or receptors for active tumor targeting [3].…”

PLGA-modified nanoparticles for the treatment of hypo-vascularized HPV-related cervical cancers.

“…into this system maintains cell populations with varying proliferative capability, contributing to chemoresistance for cell cycle-specific drugs, and replicates the diffusion limitations of bloodborne substances observed for tissue in vivo 50,59,152,183 . Accordingly, the bulk of NP uptake is expected to occur in the spheroid outer proliferative regions, as we have previously measured .…”