Paclitaxel‐Loaded Polymer Nanoparticles for the Reversal of Multidrug Resistance in Breast Cancer Cells

Novel paclitaxel‐loaded polymer nanoparticles were developed for circumventing multidrug resistance (MDR) of malignant cancerous diseases, which is an unsolved clinical problem in cancer chemotherapy. In many cases, MDR is due to the intrinsic or acquired expression of an efflux pump, the P‐170 glycoprotein (P‐gp). By encapsulating paclitaxel in a water‐soluble and biocompatible synthetic polyampholyte using a solid‐state reaction the highly water‐soluble paclitaxel‐loaded nanoparticles are formed. The resulting paclitaxel nanoparticles with an average diameter of 250 nm show a significant reversal of chemoresistance in the drug‐resistant variants (MCF7/ADR, MT3/ADR) by a factor of 100 or more. The novel paclitaxel nanoparticles enter MDR breast cancer cells by adsorptive endocytosis bypassing the P‐gp, preventing the efflux of paclitaxel and thus restoring the anti‐proliferative effect of paclitaxel.     

Cancer Detection: Polyhedral Oligomeric Silsesquioxanes‐Containing Conjugated Polymer Loaded PLGA Nanoparticles with Trastuzumab (Herceptin) Functionalization for HER2‐Positive Cancer Cell Detection (Adv. Funct. Mater. 2/2011)

The synthesis of polyhedral oligomeric silsesquioxanes (POSS)‐containing conjugated polymer (CP) and the polymer loaded poly(lactic‐co‐glycolic‐acid) (PLGA) nanoparticles (NPs) with surface antibody functionalization for human epidermal growth factor receptor 2 (HER2)‐positive cancer cell detection are reported. Due to the steric hindrance of POSS, NPs prepared from POSS‐containing CP show improved photoluminescence quantum yield as compared to that for the corresponding linear CP encapsulated NPs. In addition, the amount of ‐NH₂ groups on NP surface is well‐controlled by changing the molar ratio of poly(lactic‐co‐glycolic‐acid)‐b‐poly(ethylene glycol) (PLGA‐b‐PEG‐NH₂) to PLGA‐OCH₃ during NP formulation. Further conjugation of the NH₂‐functionalized CP NPs with trastuzumab (Herceptin) yields NPs with fine‐tuned protein density. These NPs are able to discriminate SKBR‐3 breast cancer cells from MCF‐7 breast cancer cells and NIH/3T3 fibroblast cells both on substrate and in suspension by taking advantage of the specific binding affinity between trastuzumab and HER2 overexpressed in SKBR‐3 breast cancer cell membrane. The high quantum yield and fine‐tuned surface specific protein functionalization make the POSS‐containing CP loaded NPs a good candidate for targeted biological imaging and detection.     

Solar Cells: Performance Optimization of Polymer Solar Cells Using Electrostatically Sprayed Photoactive Layers (Adv. Funct. Mater. 20/2010)

Polymer solar cells (PSCs) are fabricated using a novel film deposition method, the electrostatic spray (e‐spray) technique. Stable atomization and uniform deposition of the polymer blend by e‐spray are achieved by manipulating the solution concentration, the solvent composition, and the electric field. The performance of PSCs is primarily influenced by the inherent film morphology of the e‐sprayed polymer‐blend active layers, which is significantly different from that of the conventional films that are formed using the spin‐coating (SC) method. The intrinsically formed interfacial boundaries between the e‐sprayed blend pancakes resist charge transport, which unfavorably influences device efficiency. The internal series resistance (R_S) of the PSCs that are formed using the e‐spray method (e‐spray‐PSC) is significantly reduced by a solvent vapor soaking (SVS) treatment in addition to the conventional thermodynamic nanomorphology controls. The detailed relationship between the morphologies (film morphology and internal nanomorphology) and the R_S is revealed using impedance spectroscopy. The performance of the e‐spray‐PSCs is comparable to those of the PSCs that are fabricated using the SC method under identical conditions. Therefore, the e‐spray method can be used to fabricate ultralow‐cost PSCs, because of the performance results combined with the intrinsic advantages that the e‐spray method is simple and has a low materials loss.     

Dual‐Targeting to Cancer Cells and M2 Macrophages via Biomimetic Delivery of Mannosylated Albumin Nanoparticles for Drug‐Resistant Cancer Therapy

Multidrug resistance (MDR) is an issue that is not only related to cancer cells but also associated with the tumor microenvironments. MDR involves the complicated cancer cellular events and the crosstalk between cancer cells and their surroundings. Ideally, an effective system against MDR cancer should take dual action on both cancer cells and tumor microenvironments. The authors find that both the drug‐resistant colon cancer cells and the protumor M2 macrophages highly express two nutrient transporters, i.e., secreted protein acidic and rich in cysteine (SPARC) and mannose receptors (MR). By targeting SPARC and MR, a system can act on both cancer cells and M2 macrophages. Herein the authors develop a mannosylated albumin nanoparticles with coencapsulation of different drugs, i.e., disulfiram/copper complex (DSF/Cu) and regorafenib (Rego). The results show that combination therapy of DSF/Cu and Rego efficiently inhibits the growth of drug‐resistant colon tumor, and the combination has not been reported yet for use in anticancer treatment. The system significantly improves the treatment outcomes in the animal model bearing drug‐resistant tumors. The therapeutic mechanisms involve enhanced apoptosis, upregulation of intracellular ROS, anti‐angiogenesis, and tumor‐associated macrophage “re‐education.” This strategy is characterized by dual targeting to and the simultaneous action on cancer cells and M2 macrophages, with biomimetic codelivery of a novel drug combination.