Block Copolymer ‘Stealth’ Nanoparticles for Chemotherapy: Interactions with Blood Cells In Vitro

Abstract

Passive targeting is one of the approaches to reduce the side effects in intravenous chemotherapeutic administration. This is usually achieved by using so‐called ‘stealth’ particles as carriers, such that the particles can avoid uptake by cells of the reticulo endothelial system (RES) and thus enhance their blood lifetime. To date, there have been no studies of the contribution of various factors to the uptake of particles by the RES, although there is general agreement that a hydrophilic particle surface is helpful. In this study, data is presented on the effect of particle size and surface chemistry on the uptake by monocyte cell lines, as well as by cells in whole blood. Block copolymers of hydrophilic poly(ethylene glycol) (PEG) and the hydrophobic poly(L‐lactide) (PLA) have been used to study surface concentration and conformation effects. It is found that diblock copolymers, in general, show the best stealth characteristics, although triblocks with PEG segment lengths above a certain value are also comparable. It is also found that the uptake goes through a minimum with respect to particle size. For the first time, a method is presented to evaluate the relative uptake efficiency of various types of blood cells, using flow cytometry. The observations are related to structural features found on the polymers.

Polyphosphazene nanoparticles for cytoplasmic release of doxorubicin with improved cytotoxicity against Dox-resistant tumor cells

“…Multifunctional nanostructured drug carriers, constructed through skillful integration of polymeric materials and drugs, have been proposed to break through biological barriers and deliver cargo drugs to specific sites, especially to solid tumors [2][3][4][5][6][7][8]. By an enhanced permeability and retention (EPR) effect, these nanosized delivery systems are able to passively accumulate drugs in solid tumors [9][10][11][12][13].…”

Inorganic Drug‐Delivery Nanovehicle Conjugated with Cancer‐Cell‐Specific Ligand

“…[1,2] For these reasons, during the past few decades, a great deal of effort has been devoted to invent and discover novel medicinal approaches, including drug-delivery system (DDS). [3][4][5][6][7][8][9][10][11] Many drug-delivery vectors, either viral or nonviral, have been developed in order to improve the performance of many existing anticancer drugs through enhancing their efficacy as well as cellular uptake efficiency to malignant tumor cells. The rapid development in nanotechnology enabled controlled design and synthesis of supramolecular-sized materials and, furthermore, nano-bio convergences open a new era and suggest many possible ways to settle the concerns in cancer chemotherapy.…”

Hydrophilic mesoporous carbon nanospheres with high drug-loading efficiency for doxorubicin delivery and cancer therapy

“…After loading with DOX, the oMCN@DOX was subsequently wrapped up by DSPE-mPEG2000 with hydrophobic segments physically absorbed on the surface of the oMCNs and hydrophilic parts as the outer layers, which helped to avoid the recognition of reticuloendothelial system. [15][16][17] In order to confirm that hydrophilic groups and polyethylene glycol were successfully introduced to the MCNs, the FTIR and 1 H-nuclear magnetic resonance spectra were collected, as shown in Figure 2. From the FTIR spectra (Figure 2A), it can be clearly seen that the MCNs exhibited typical related absorption bands of aromatic hydrocarbons at 2,025 cm So the results of FTIR spectra showed that we had succeeded in synthesizing oMCN@PEG.…”