Water-insoluble Anticancer Drug Research Articles

PH-Responsive Water-Soluble Chitosan Amphiphilic Core–Shell Nanoparticles: Radiation-Assisted Green Synthesis and Drug-Controlled Release Studies

This work aims to apply water radiolysis-mediated green synthesis of amphiphilic core-shell water-soluble chitosan nanoparticles (WCS NPs) via free radical graft copolymerization in an aqueous solution using irradiation. Robust grafting poly(ethylene glycol) monomethacrylate (PEGMA) comb-like brushes were established onto WCS NPs modified with hydrophobic deoxycholic acid (DC) using two aqueous solution systems, i.e., pure water and water/ethanol. The degree of grafting (DG) of the robust grafted poly(PEGMA) segments was varied from 0 to ~250% by varying radiation-absorbed doses from 0 to 30 kGy. Using reactive WCS NPs as a water-soluble polymeric template, a high amount of DC conjugation and a high degree of poly(PEGMA) grafted segments brought about high moieties of hydrophobic DC and a high DG of the poly(PEGMA) hydrophilic functions; meanwhile, the water solubility and NP dispersion were also markedly improved. The DC-WCS-PG building block was excellently self-assembled into the core-shell nanoarchitecture. The DC-WCS-PG NPs efficiently encapsulated water-insoluble anticancer and antifungal drugs, i.e., paclitaxel (PTX) and berberine (BBR) (~360 mg/g). The DC-WCS-PG NPs met the role of controlled release with a pH-responsive function due to WCS compartments, and they showed a steady state for maintaining drugs for up to >10 days. The DC-WCS-PG NPs prolonged the inhibition capacity of BBR against the growth of S. ampelinum for 30 days. In vitro cytotoxicity results of the PTX-loaded DC-WCS-PG NPs with human breast cancer cells and human skin fibroblast cells proved the role of the DC-WCS-PG NPs as a promising nanoplatform for controlling drug release and reducing the side effects of the drugs on normal cells.

Tumor Targeting by Conjugation of Chlorambucil with Zwitterionic Near-Infrared Fluorophore for Cancer Phototherapy.

Improving the tumor targeting of anticancer drugs to minimize systemic exposure remains challenging. The chemical conjugation of anticancer drugs with various near-infrared (NIR) fluorophores may provide an effective approach to improve NIR laser-induced cancer phototherapy. Towards this end, the selection of NIR fluorophores conjugated with hydrophobic anticancer drugs is an important consideration for targeted cancer photothermal therapy (PTT). In this study, a highly water-soluble zwitterionic NIR fluorophore (ZW800) was prepared to conjugate with a water-insoluble anticancer drug, chlorambucil (CLB), to improve tumor targeting, in vivo biodistribution, and PTT performance. The in vivo results using an HT-29 xenograft mouse model demonstrated that the CLB-ZW800 conjugate not only exhibited high tumor accumulation within 4 h after injection, but also showed rapid body clearance behavior for less systemic toxicity. Furthermore, the tumor tissue targeted by the CLB-ZW800 conjugate was exposed to 808 nm NIR laser irradiation to generate photothermal energy and promote apoptotic cell death for the effective PTT of cancer. Therefore, this study provides a feasible strategy for developing bifunctional PTT agents capable of tumor-targeted imaging and phototherapy by the conjugation of small molecule drugs with the versatile zwitterionic NIR fluorophore.

Calcium chloride linked camel milk derived casein nanoparticles for the delivery of sorafenib in hepatocarcinoma cells

Sorafenib, a multikinase inhibitor used for the treatment of hepatocellular carcinoma, is limited by its low oral bioavailability. To overcome this drawback, we have developed novel camel milk casein-derived nanoparticles as a drug delivery system. Camel milk casein is not only biocompatible on oral administration but is actually a dietary protein of pharmaceutical relevance. Casein is used because of its amphiphilic nature, self-assembling property, ability to show sustained release, and capability of encapsulating both hydrophilic and hydrophobic drugs. In this study, camel milk casein nanoparticles loaded with sorafenib were developed and characterized. Characterization of casein nanoparticles was done by dynamic light scattering (DLS), zeta potential analysis, scanning light microscopy (SEM), and FTIR. The drug content in nanoparticle and drug-protein binding studies were conducted by UV spectroscopy. The cytotoxicity and cellular uptake efficiency studies were performed in HepG2 cell lines. It was observed that the cytotoxic effect of sorafenib loaded camel milk casein nanoparticles was more than free sorafenib in HepG2 cells. This work suggests camel milk casein as a suitable drug delivery molecule for sorafenib. In the future, it may also be used in enhancing the efficacy and specific distribution of other water-insoluble anticancer drugs.

Calcium chloride linked camel milk derived casein nanoparticles for the delivery of sorafenib in hepatocarcinoma cells

Sorafenib, a multikinase inhibitor used for the treatment of hepatocellular carcinoma, is limited by its low oral bioavailability. To overcome this drawback, we have developed novel camel milk casein-derived nanoparticles as a drug delivery system. Camel milk casein is not only biocompatible on oral administration but is actually a dietary protein of pharmaceutical relevance. Casein is used because of its amphiphilic nature, self-assembling property, ability to show sustained release, and capability of encapsulating both hydrophilic and hydrophobic drugs. In this study, camel milk casein nanoparticles loaded with sorafenib were developed and characterized. Characterization of casein nanoparticles was done by dynamic light scattering (DLS), zeta potential analysis, scanning light microscopy (SEM), and FTIR. The drug content in nanoparticle and drug-protein binding studies were conducted by UV spectroscopy. The cytotoxicity and cellular uptake efficiency studies were performed in HepG2 cell lines. It was observed that the cytotoxic effect of sorafenib loaded camel milk casein nanoparticles was more than free sorafenib in HepG2 cells. This work suggests camel milk casein as a suitable drug delivery molecule for sorafenib. In the future, it may also be used in enhancing the efficacy and specific distribution of other water-insoluble anticancer drugs.

Solubilization of Paclitaxel by Self-Assembled Amphiphilic Phospholipid-Mimetic Polymers with Varied Hydrophobicity.

2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers have been used as a coating agent on medical devices and as a carrier in drug delivery systems (DDSs). Paclitaxel (PTX) is a water-insoluble anticancer drug whose solubilizer is necessary for administration. Block and random copolymers composed of hydrophilic MPC and butyl methacrylate, named PMB, show different properties, depending on the polymer sequence and MPC content. In the present study, we used amphiphilic MPC polymers comprising hydrophobic dodecyl methacrylate (DMA). The self-assembling properties and PTX solubilization of random and block poly(MPC-co-DMA)s (rPMDs and bPMDs) with different compositions were examined and compared. rPMDs with high DMA content formed large and relatively loose self-assembled structures, which solubilized PTX. However, bPMDs formed small and compact self-assembled structures with poor PTX solubilization. PTX solubilized by PMB with small and loose self-assembled structures showed efficient drug action, similar to free PTX; however, rPMDs fell short of demonstrating PTX efficiency. Our results suggest that the self-assembling properties and the hydrophobicity of amphiphilic MPC polymers largely affect PTX solubilization as well as drug action, which is required to be controlled by the polymer sequence, as well as the structure and composition of the hydrophobic monomer for efficient DDS.

Near-infrared stimulated hydrogel patch for photothermal therapeutics and thermoresponsive drug delivery

Nanotechnology driven cancer theranostics hold potential as promising future clinical modalities. Currently, there is a strong emphasis on the development of combinational modalities, especially for cancer treatment. In this study, we present a topical hydrogel patch for nanomaterial-assisted photothermal therapeutics as well as for on-demand drug delivery application. The patch was derived from interpenetrating networks (IPNs) of alginate (Alg) and polyacrylamide (PAAm) in weight ratio 8:1 by free radical polymerization. The patch interiors were composed of hybrid nanostructures derived from gold nanorods (AuNRs) anchored onto polyvinylpyrrolidone (PVP) functionalized graphene oxide (PVP-nGO) to form PVP-nGO@AuNRs hybrids. Field emission scanning electron microscopy (FE-SEM) images revealed the porous nature of the hybrid hydrogel patch with an average pore size of ~28.60 ± 3.10 μm. Besides, functional characteristics of the hybrid patch, such as mechanical strength, viscoelastic and swelling behavior, were investigated. Under near-infrared (NIR) radiation exposure, the hybrid patch exhibited photothermal properties such as surface temperature rise to 75.16 ± 0.32 °C, sufficient to ablate cancer cells thermally. Besides, the heat generated in the hybrid patch could be transmitted to an underlying hydrogel (mimicking skin tissue) when stacked together without much loss. Under cyclic photothermal heating, the patch could retain its photothermal stability for four cycles. Furthermore, the hybrid patch demonstrated NIR stimulated drug release, which was evaluated using methotrexate (MTX, water-insoluble anticancer drug) and rhodamine B (RhB, water-soluble dye). Taken together, this work provides a new dimension towards the development of externally placed hydrogel patches for thermal destruction of localized solid tumors and tunable delivery of chemotherapeutic drugs at the target site.

Biodegradable β-Cyclodextrin Conjugated Gelatin Methacryloyl Microneedle for Delivery of Water-Insoluble Drug.

Transdermal delivery of water-insoluble drugs via hydrogel-based microneedle (MN) arrays is crucial for improving their therapeutic efficacies. However, direct loading of water-insoluble drug into hydrophilic matrices remains challenging. Here, a biodegradable MN array patch that is fabricated from naturally derived polymer conjugates of gelatin methacryloyl and β-cyclodextrin (GelMA-β-CD) is reported. When curcumin, an unstable and water-insoluble anticancer drug, is loaded as a model drug, its stability and solubility are improved due to the formation of an inclusion complex. The polymer-drug complex GelMA-β-CD/CUR can be formulated into MN arrays with sufficient mechanical strength for skin penetration and tunable drug release profile. Anticancer efficacy of released curcumin is observed in three-dimensional B16F10 melanoma models. The GelMA-β-CD/CUR MN exhibits relatively higher therapeutic efficacy through more localized and deeper penetrated manner compared with a control nontransdermal patch. In vivo studies also verify biocompatibility and degradability of the GelMA-β-CD MN arrays patch.

Cell uptake and anti-tumor effect of liposomes containing encapsulated paclitaxel-bound albumin against breast cancer cells in 2D and 3D cultured models

Paclitaxel (PTX), a water insoluble anticancer drug, was incorporated into the inner aqueous core of a liposome without the aid of an organic co-solvent, via non-covalent binding with bovine serum albumin (BSA) to form a PTX-BSA liposome. In the present study, PTX-BSA-liposomes are shown to have potent effects on human-derived breast cancer cell lines, MCF-7 cells and MDA-MB-231 cells, in 2D monolayer cultured cells and 3D multicellular tumor spheroids. The results of cellular uptake studies in 2D monolayer cultured cells clearly showed that the fluorescence derived from dansyl-l-asparagine (DNSA), a model encapsulated drug, and Cy5-cholesterol (a model membrane) of DNSA-BSA-liposome were observed inside the cells. Along with cell uptake, the PTX-BSA-liposomes exhibited a concentration-dependent cytotoxicity against MCF-7 and MDA-MB-231 cells but the IC50 value of the PTX-BSA-liposomes was higher than that of free PTX and nab-PTX (albumin-bound PTX nanoparticle). On the other hand, PTX-BSA-liposome, as in the cases of free PTX and nab-PTX, inhibited cell growth in both 3D MCF-7 and MDA-MB-231 tumor spheroids, indicating that PTX-BSA-liposomes penetrated into the tumor spheroid. These results suggest that PTX-BSA-liposomes are an organic solvent free PTX formulation that would have potent anti-proliferative effects against breast cancer.

Synthesis, characterization, and antileukemic activity of new water-soluble analogs of prodimin

Two new compounds from the class of bis(3-halopropionyl)amides were synthesized by the reaction of 3-halopropionyl chloride with N,N′-dimethylethylenediamine. These structural analogs of prodimin, a water insoluble anticancer drug, are soluble in water, which significantly expands methods for their administration into a body. The compounds obtained and prodimin (as a reference substance) were studied on P388 murine leukemia and some of its drug-resistant strains. The data obtained suggest a high efficacy of one synthesized compound against drug-resistant tumors.

Encapsulation and Enhanced Delivery of Topoisomerase I Inhibitors in Functionalized Carbon Nanotubes.

The topoisomerase I inhibitors SN-38 and camptothecin (CPT) have shown potent anticancer activity, but water insolubility and metabolic instability limits their clinical application. Utilizing carbon nanotubes as a protective shell for water-insoluble SN-38 and CPT while maintaining compatibility with aqueous media via a carboxylic acid-functionalized surface can thus be a strategy to overcome this limitation. Through hydrophobic–hydrophobic interactions, SN-38 and CPT were successfully encapsulated in carboxylic acid functionalized single-walled carbon nanotubes and dispersed in water. The resulting cell proliferation inhibition and drug distribution profile inside the cells suggest that these drug-encapsulated carbon nanotubes can serve as a promising delivery strategy for water-insoluble anticancer drugs.

Injectable Coacervate Hydrogel for Delivery of Anticancer Drug-Loaded Nanoparticles in vivo.

In this study, bortezomib (BTZ, a cytotoxic water-insoluble anticancer drug) was encapsulated in micellar nanoparticles having a catechol-functionalized polycarbonate core through a pH-sensitive covalent bond between phenylboronic acid (PBA) in BTZ and catechol, and these drug-loaded micelles were incorporated into hydrogels to form micelle/hydrogel composites. A series of injectable, biodegradable hydrogels with readily tunable mechanical properties were formed and optimized for sustained delivery of the BTZ-loaded micelles through ionic coacervation between PBA-functionalized polycarbonate/poly(ethylene glycol) (PEG) "ABA" triblock copolymer and a cationic one having guanidinium- or thiouronium-functionalized polycarbonate as "A" block. An in vitro release study showed the pH dependence in BTZ release. At pH 7.4, the BTZ release from the micelle/hydrogel composite remained low at 7%, whereas in an acidic environment, ∼85% of BTZ was released gradually over 9 days. In vivo studies performed in a multiple myeloma MM.1S xenograft mouse model showed that the tumor progression of mice treated with BTZ-loaded micelle solution was similar to that of the control group, whereas those treated with the BTZ-loaded micelle/hydrogel composite resulted in significant delay in the tumor progression. The results demonstrate that this hydrogel has great potential for use in subcutaneous and sustained delivery of drug-loaded micelles with superior therapeutic efficacy.

Controlled Release of Curcumin via Folic Acid Conjugated Magnetic Drug Delivery System

In the paper, folic acid(FA)-mediated and β-cyclodextrin(β-CD) derivatives functionalized magnetic Fe3O4 nanoparticles(MNPs) were successfully prepared as drug carriers for the targeted delivery and controlled release of water-insoluble anticancer drug. FA-sulfobutyl ether-β-CD-MNPs(FA-SBE-β-CD-MNPs), FA-hydroxypropyl-β-CD-MNPs(FA-HP-β-CD-MNPs) and FA-carboxymethyl-β-CD-MNPs(FA-CM-β-CD-MNPs) were fabricated, and the loading efficiency and relative entrapment rate of curcumin are 12.04 mg/g, 95.56% for FA-SBE-β-CD-MNPs, 9.6 mg/g, 81.63% for FA-HP-β-CD-MNPs and 7.88 mg/g, 85.28% for FA-CM-β-CD-MNPs, respectively. Meanwhile, at pH=5.0, the optimal release rate of curcumin is about 46.07% for FA-SBE-β-CD-MNPs in 5 h. Cellular uptake indicates that curcumin can be selectively transported to targeting site and released from the internalized carriers. The in vitro cytotoxicity reveals that non-toxic FA-SBE-β-CD-MNPs have excellent biocompatibility on HepG2 cells in the tested concentrations. Therefore, FA-SBE-β-CD-MNPs could provide a promising platform for the targeting delivery of water insoluble anti-cancer drugs for different treatment needs of cancer therapy.

Combined Adsorption and Covalent Linking of Paclitaxel on Functionalized Nano-Graphene Oxide for Inhibiting Cancer Cells.

Developing targeted delivery nanosystems for delivering chemotherapeutic anticancer drugs specifically to cancerous tissues with improvement in the specificity of drugs for different cancer cells can result in high therapeutic efficacy and low toxicity in healthy tissues. Herein, we proposed the synthesis of a multifunctional nanodelivery system, folic acid (FA) decorating nanographene oxide (nGO) functionalized with poly(ethylene glycol) (PEG), called pGO-FA, with good biocompatibility and good delivering performance of a hydrophobic water-insoluble anticancer drug of paclitaxel (PTX). 4-br-PEG-NH2, FA, and PTX were attached to PEG-functionalized nGO (pGO) through a combined chemical and physical force to form a nanosized complex, pGO-FA-PTX, defined as the nanodrug system. WST-8 assay in vitro illustrated that pGO-FA-PTX inhibited A2780 cells in a concentration-dependent manner. Cell viability was kept high to 60% when treated with 200 nM of free PTX. However, pGO-FA-PTX with the same dose of PTX (cell viability less than 30%) had double the cytotoxicity effect compared to free PTX. Furthermore, fluorescence observation demonstrated that pGO-FA-PTX exhibited an improved efficiency in killing A2780 cells due to the special affinity between FA and FA receptor, which has high expression in cancer cells. The strategy and method used in this study could be effective in improving both the bioavailability of PTX and therapy efficiency.

Adaptive Chitosan Hollow Microspheres as Efficient Drug Carrier.

Smart drug carrier with function-oriented adaptations is highly desired due to its unique properties in medical applications. Herein, adaptive chitosan hollow microspheres (CHM) are fabricated by employing interfacial Schiff-base bonding reaction. Hydrophilic macromolecules of glycol chitosan are fixed at the oil/water interface through numerous hydrophobic small molecules of borneol 4-formylbenzoate, forming the CHM with a positively charged surface and lipophilic cavity. These CHM have an average size of 400-1000 nm after passing through the 0.22 μm apertures of filter paper. This phenomenon combined with SEM measurements demonstrates its remarkable shape-adaptive behavior. Furthermore, the CHM present a pH-dependence of structural stability. When pH value reduces from 7.06 to 5.01, the CHM begin to lose their integrity. All those characteristics make the CHM an intelligent drug carrier, especially for water-insoluble anticancer drugs, paclitaxel (PTX) in particular. Both cell uptake and cell cytotoxicity assays suggest that the PTX-loaded CHM are highly efficient on HepG2 and A549 cells. Therefore, rather than most of the traditional materials, these adaptive CHM show great potential as a novel drug carrier.

Synthesis and characterization of 3,6-O,O’- dimyristoyl chitosan micelles for oral delivery of paclitaxel

The aim of the present study was to investigate the potential application of 3,6-O,O’- dimyristoyl chitosan DMCh, an amphiphilic derivative of chitosan, for improving the oral bioavailability of paclitaxel (PTX), a water insoluble anticancer drug. The O-acylation of chitosan with myristoyl chloride was carried out by employing high (≈13.3) or low (2.0) molar excess of chitosan to result in samples DMCh07 and DMCh12, respectively. The successful O-acylation of chitosan was confirmed by FTIR and 1H NMR spectroscopy, the latter allowing also the determination of average degree of substitution (DS). The critical aggregation concentration (CAC) of samples DMCh07 (DS≈6.8%) and DMCh12 (DS≈12.0%) were 8.9×10−3mg/mL and 13.2×103mg/mL, respectively. It was observed by TEM that the DMCh micelles showed spherical shape while DLS measurements allowed the determination of their average size (287nm–490nm) and zeta potential (+32mV to +44mV). Such DMCh micelles were able to encapsulate paclitaxel with high drug encapsulation efficiency (EE), as confirmed by HPLC analyses. Studies on the cytotoxicity of DMCh07 micelles toward Caco-2 and HT29-MTX cells showed that, regardless the PTX loaded, DMCh07 micelles slightly decreased cellular viability at low micelles concentration (≤1μg/mL) while at high concentration (>10μg/mL) PTX-loaded DMCh07 micelles were less toxic toward Caco-2 cells when compared to free PTX. The PTX permeation across Caco-2 monoculture and Caco-2/HT29-MTX co-culture model confirmed the potential of DMCh micelles in improving the intestinal absorption of PTX. These results suggest that DMCh micelles may be a promising carrier to encapsulate PTX aiming cancer therapy.

Preparation and characterization of mesoporous bioactive glass from agricultural waste rice husk for targeted anticancer drug delivery

Mesoporous bioactive glass (MBG) possesses excellent biocompatibility and an important material used for bone regeneration and drug delivery. The aim of this study is to synthesize MBG from low-cost agricultural waste rice husk (rMBG) using a sol-gel process. We show that rMBG has typical characteristics of the well-ordered hexagonal mesostructure of MBG and can be grafted with folic acid (FA) and then loaded with anticancer drugs for targeting cancer cells. By loading rMBG-FA with camptothecin (CPT, a water-insoluble anticancer drug) we formed rMBG-FA/CPT, which killed cancer cells by being selectively and efficiently taken in via the cells’ FA receptors (FRs). We found that rMBG-FA/CPT showed a higher cytotoxicity to FR-overexpressed HeLa cells than to FR-deficient L929 cells. Our results indicate that low-cost rMBG offers a potentially practical medical application that can replace highly valuable MBG as well as reduce environmental pollution caused by agricultural waste.

The use of surfactants to enhance the solubility and stability of the water-insoluble anticancer drug SN38 into liquid crystalline phase nanoparticles

Cubosomes were used to increase the aqueous solubility of the water insoluble anticancer drug SN38. The results showed that the use of a common cubosome formulation consisting of phytantriol (PHYT) as the matrix amphiphile (PHYT-cubosome) led to a 6-fold increase in the solubility of SN38. However, mean hydrodynamic diameter (DH) and polydispersity index (PDI) of these PHYT-cubosome particles were 345±49nm and 0.37±0.05, respectively, making them unsuitable for intravenous applications. Several additives were investigated to increase the solubility of SN38 and reduce the DH and PDI values of the resulting particles. Charged additives such as didodecyldimethyl ammonium bromide (DDAB) and sodium dodecyl sulfate (SDS) led to improvements in the physiochemical properties of the cubosomes. Notably, the PHYT-DDAB and PHT-SDS cubosomes led to 15- and 14-fold increases in the aqueous solubility of SN38, respectively. Moreover, the SN38 loaded into the PHYT-DDAB and PHYT-SDS cubosomes was found to be highly stable, with very little hydrolysis to its inactive acid form. In summary, the addition of DDAB and SDS to PHYT-cubosome nanoparticle drug delivery systems not only led to considerable improvements in their physiochemical properties, but also enhanced the aqueous solubility of SN38 and increased its chemical stability.

Paclitaxel and curcumin co-bound albumin nanoparticles having antitumor potential to pancreatic cancer

Albumin nanoparticles are considered to be an effective way to load water-insoluble anticancer drugs and target tumors via the gp60-mediated pathway. Herein, we fabricated an albumin nanoparticle formulation for co-loading paclitaxel (PTX) and curcumin (CCM), both of which have prominent anticancer efficacy, via nanoparticle albumin-bound (NabTM) technology using high-pressure homogenization. The PTX/CCM co-bound albumin nanoparticles (PTX/CCM Alb-NPs) had a slightly greater particle size of ~250 nm than that of plain PTX Alb-NPs and CCM Alb-NPs (~234 and ~134 nm, respectively), with spherical surface morphology and stable size maintenance. However, the zeta potential of PTX/CCM Alb-NPs (ca. −30 mV) was not significantly different from that of PTX or CCM Alb-NPs. The loaded PTX and CCM were released gradually from the PTX/CCM Alb-NPs over ~24 h (97.7 ± 1.7% and 76.2 ± 0.5%, respectively). Furthermore, PTX/CCM Alb-NPs appeared to be efficiently internalized into Mia Paca-2 cells and exhibited a 71% increased IC50 versus PTX Alb-NPs in terms of cytotoxicity to Mia Paca-2 cells. These results suggest that PTX/CCM Alb-NPs are a new potential anticancer agent for combination therapy.

Dual Functional Nanocarrier for Cellular Imaging and Drug Delivery in Cancer Cells Based on π-Conjugated Core and Biodegradable Polymer Arms.

Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent π-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV π-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ∼150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross-talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment. The new nanocarrier approach reported in the present manuscript accomplishes both cellular imaging and delivering drugs to intracellular compartments in a single polymer system. The present investigation is one of the first examples to demonstrate the dual functional biodegradable luminescence nanocarrier concept in the literature, and the studies established this proof-of-concept in cellular imaging and drug delivery in cancer cells.

Polymeric micelles stabilized by polyethylenimine–copper (C2H5N–Cu) coordination for sustained drug release

Polymeric micelles stabilized by polyethylenimine–copper (C2H5N–Cu) coordination were described to improve the release property of water-insoluble anticancer drug.