Delivery Of Hydrophobic Anticancer Drugs Research Articles

Stimuli-responsive gel-micelles with flexible modulation of drug release for maximized antitumor efficacy

Engineered stimuli-responsive drug delivery devices hold vast promise in biological applications for disease treatment due to their maximized therapeutic efficacy. In this study, a novel, stably cross-linked, and pH-sensitive biodegradable gel-micelle was constructed with amphiphilic conjugates of trimethylene dipiperidine-methacrylic anhydride-hyaluronic acid-stearylamine (TMDP-MA-HA-SA, TMHS) to improve tumor-targeting with flexible intracellular delivery of paclitaxel (PTX).The cross-linked methacrylate bonds significantly improved the biostability of TMHS gel-micelle (~ 200 nm) over the non-cross-linked under physiological conditions, while hyaluronic acid plays an important role in active tumor targetability. The gradual degradation of cross-linked hyaluronic acid shell was triggered by the concentrated hyaluronidase. Meanwhile, under acidic conditions (pH < 6.5), the tertiary amines of pH-sensitive TMDP moieties were protonated and thereby solubilized the gel-micellar core-portions. The resultant pH-triggered inner-core spaces rapidly prompted PTX release in the presence of multiple cytosolic enzymes that mainly degraded the remaining hydrophobic stearylamine core. During the in vitro cytotoxicity assay, PTX-loaded TMHS gel-micelles (CLTMHSPTX) revealed anticancer efficacy against human hepatocellular carcinoma HepG2 cells with IC50 of 1.42 μg/mL (PTX concentration), significantly lower than other groups. In parallel, the in vivo anti-tumor efficacy of CLTMHSPTX gel-micelles against BALB/c xenograft tumor animal model demonstrated the greater tumor growth inhibition capacity of 72.06%, compared to other treatment groups at a safe concentration. Consequently, the cross-linked and stimuli-responsive CLTMHSPTX gel-micelles hold a great potential for flexible modulation of intracellular delivery of hydrophobic anticancer drugs with maximized antitumor efficacy.

Dual redox/pH-responsive hybrid polymer-lipid composites: Synthesis, preparation, characterization and application in drug delivery with enhanced therapeutic efficacy

The development of intelligent drug delivery system that can efficiently deliver drug to targeted site and release the cargo in a controlled manner is of great significance for cancer chemotherapy. In the present study, dual redox/pH-sensitive amphiphilic copolymer, cholesterol modified poly (β-amino esters)-grafted disulfide poly (ethylene glycol) methyl ether (PAE(-ss-mPEG)-g-Chol), is successfully synthesized via Michael-type step polymerization using disulfide linkage-containing PEG segment. PEGylated lipid is introduced to fabricate the doxorubicin (DOX)-loaded hybrid polymer-lipid nanoparticles (NPs) with (DOX-HDPLNPs) or without (DOX-HPLNPs) disulfides to receive stable NPs with enhanced loading capacity and improved cellular uptake ability as well as serum stability. The HDPLNPs show not only pH-sensitivity because of poly(β-amino esters) (PAE) residues in main chain but also the redox-responsivity due to the disulfides on the side chains with PEG segments. As expected, the DOX-HDPLNPs exhibited the extended blood circulation time and higher serum stability in normal physiological environment, but once deposited in the tumor microenvironment (e.g. low pH value and high GSH concentration), they underwent a dramatic size transition and charge reversal. These features not only can facilitate the NPs accumulation through the enhanced permeability and retention (EPR) effect and endocytosis by tumor cells but also realize the drug controlled release and more efficient tumor inhibition. The in vitro and in vivo results demonstrate that the DOX-HDPLNPs possess the highest therapeutic efficacy with high cellular uptake and negligible cytotoxicity compared to the controls and free drug. Therefore, the HDPLNPs have good potential as smart delivery platforms for hydrophobic anticancer drug delivery due to high uptake by tumor cells and redox/pH-triggered drug release.

Enhancing Docetaxel Delivery to Multidrug-Resistant Cancer Cells with Albumin-Coated Nanocrystals.

Intravenous delivery of poorly water-soluble anticancer drugs such as docetaxel (DTX) is challenging due to the low bioavailability and the toxicity related to solubilizing excipients. Colloidal nanoparticles are used as alternative carriers, but low drug loading capacity and circulation instability limit their clinical translation. To address these challenges, DTX nanocrystals (NCs) were prepared using Pluronic F127 as an intermediate stabilizer and albumin as a functional surface modifier, which were previously found to be effective in producing small and stable NCs. We hypothesize that the albumin-coated DTX NCs (DTX-F-alb) will remain stable in serum-containing medium so as to effectively leverage the enhanced permeability and retention effect. In addition, the surface-bound albumin, in its native form, may contribute to cellular transport of NCs through interactions with albumin-binding proteins such as secreted protein acidic and rich in cysteine (SPARC). DTX-F-alb NCs showed sheet-like structure with an average length, width, and thickness of 284 ± 96, 173 ± 56, and 40 ± 8 nm and remained stable in 50% serum solution at a concentration greater than 10 μg/mL. Cytotoxicity and cellular uptake of DTX-F-alb and unformulated (free) DTX were compared on three cell lines with different levels of SPARC expression and DTX sensitivity. While the uptake of free DTX was highly dependent on DTX sensitivity, DTX-F-alb treatment resulted in relatively consistent cellular levels of DTX. Free DTX was more efficient in entering drug-sensitive B16F10 and SKOV-3 cells than DTX-F-alb, with consistent cytotoxic effects. In contrast, multidrug-resistant NCI/ADR-RES cells took up DTX-F-alb more than free DTX with time and responded better to the former. This difference was reduced by SPARC knockdown. The high SPARC expression level of NCI/ADR-RES cells, the known affinity of albumin for SPARC, and the opposing effect of SPARC knockdown support that DTX-F-alb have exploited the surface-bound albumin-SPARC interaction in entering NCI/ADR-RES cells. Albumin-coated NC system is a promising formulation for the delivery of hydrophobic anticancer drugs to multidrug-resistant tumors.

Delivery of Hydrophobic Anticancer Drugs by Hydrophobically Modified Alginate Based Magnetic Nanocarrier

Since most of the anticancer drugs have low solubility in water, the clinical use of them is limited unless by some modification the solubility increases or the drug is carried with a soluble compartment. To solve this problem, we prepared a magnetic nanocarrier with a hydrophobic surface based on oleic acid chains in which hydrophobic drug molecules such as doxorubicin hydrochloride (DOX) and paclitaxel (PTX) are easily adsorbed onto the surface. Since the drug molecules are physically adsorbed on the surface, large amounts of DOX (282 mg·g–1) and PTX (316 mg·g–1) were immobilized onto the nanocarrier. Then, the surface of the drug loaded magnetic core was covered by a smart pH-sensitive shell based on sodium alginate. The alginate shell around the magnetic core increased the stability and biocompatibility of the drug loaded nanocarrier. The results of the drug release profile showed that the drug molecules were released faster in acidic medium than in the neutral medium. The MTT assay of the nanocarrier...

Nanotechnology: An Emerging Therapeutic Option for Breast Cancer

The pharmacological application of nanodevices and systems is a rapidly emerging nanotechnology that is raising new possibilities in the diagnosis and therapy of different diseases. Nanotechnology has been providing promising tools for chemotherapy especially in cancer treatment. Nanotechnology deals with physical and biochemical properties of nanoparticles in the clinical application of drugs. Targeted nanoparticle drug delivery is intended to reduce the side effects of anticancer drugs with both decreases in consumption and treatment expenses, which are the major hurdles in conventional cancer treatment. The characteristic small size and special coating of nanoparticles facilitates the delivery of hydrophobic anticancer drugs to specific sites with reduced opsonization by defense mechanisms of the body. One of the vast applications of nanotechnology is the diagnosis, treatment, and prevention of breast cancers. Breast cancer is associated with high morbidity and mortality and is the second leading cause of death in Western countries. A large number of nanoparticles have been developed, specifically targeting metastasized tumors of the breast. The present review focuses on the application of different types of nanoparticles including gold, polymeric, and magnetic nanoparticles in the treatment of breast cancer.

P33 Inorganic nanostructures for hydrophobic anticancer drug delivery

Many drug candidates identified from natural products are poorly water-soluble. Nanotechnology provides an alternative strategy for delivery of anticancer drugs. Herein, different inorganic nanostructures such as superparamagnetic iron oxide and gold nanoparticles are utilized as the hydrophobic anticancer drug carriers. The hydrophobic anticancer drugs such as curcumin and gambogic acid were loaded into the porous area or onto the surface of the nanoparticles. Cellular uptake and biocompatibility of the nanoparticles was studied in human glioblastoma U-87 MG cells. The synthesized nanoparticles were readily internalized by U-87 MG cells. The nanoparticle-based drug carrier provides the aqueous dispersions of the hydrophobic drugs. In endosomes/lysosomes mimicking buffers with pH values of 4.5 ∼ 5.5, pH-dependent drug release was observed from drug loaded nanoparticles. The intracellular drug content and cytotoxicity were significantly higher for drug loaded nanoparticles than that of free drug. Furthermore, photothermal treatment had a synergistic effect on the drug’s anticancer activity. These results suggest that inorganic nanostructures may be a promising intracellular carrier for hydrophobic anticancer drugs. Acknowledgements This work was supported by the Macau Science and Technology Development Fund (FDCT) (Project No. 014/2014/A1).

Cellulose-graft-poly(methyl methacrylate) nanoparticles with high biocompatibility for hydrophobic anti-cancer drug delivery

Cellulose-based nanoparticles have very fine application foreground in drug delivery. Herein, a new cellulose–hydrophobic polymer hybrid nanoparticle (CE-g-PMMA NPs) with low polydispersity index has been builted by an easy method. The obtained nanoparticles with 2029wt% of PMMA possessed appropriate size (∼120nm), high drug loading efficiency (∼20wt% BA) and a slow drug release rate. The CE-g-PMMA NPs not only showed excellent biocompatibility, More important, compared to the free betulinic acid (BA), the BA-loaded CE-g-PMMA NPs significantly improved the cellular cytotoxicity and reduced the risk of side-effect. This cellulose-based “green nanoparticles” showed highly potential for hydrophobic anti-cancer drug delivery.

Synthesis and micellization of block copolymer based on host–guest recognition and double disulphide linkage for intracellular drug delivery

Block copolymer CSO2500-β-CD-PLA3000 and CSO2500-β-CD-PLA5000 were synthesized via H-bonding-instructed double disulfide linkage and host–guest recognition between adamantane and β-cyclodextrin. Transmission electron microscopy and dynamic light scattering results further confirmed the formation of self-assembled micelles with an average size of 45 and 96 nm, and a polydispersity index of 0.178 and 0.161 for blank micelles, respectively. The copolymers CSO2500-β-CD-PLA3000 and CSO2500-β-CD-PLA5000 exhibited a low critical micellization concentration of 0.041 and 0.027 mg/mL, respectively, suggesting that the micelles are highly stable in dilute solution. Doxorubicin (DOX), a hydrophobic model anticancer drug, was loaded in the micelles, and the drug release can be triggered and significantly accelerated in reductive environment. The blank micelles had fairly low cytotoxicity, but the DOX-loaded micelles exhibited great proliferation inhibition against HeLa cells, which was confirmed by MTT assay. The experimental results demonstrated that these copolymeric micelles are promising carriers for the redox-responsive intracellular delivery of hydrophobic anticancer drugs. Due to the noncovalent interactions between the host and guest, which endowed supramolecular block copolymer with the ability of reversible assembling and disassembling, dual stimuli responsiveness can be expected for this novel supramolecular block copolymer CSO2500-β-CD-PLA5000 favorable in efficient anticancer drug delivery.

Dynamic covalent linked triblock copolymer micelles for glutathione-mediated intracellular drug delivery

Redox-responsive linkages dispersed in the backbones of the synthetic polymers, while young in the current spectrum of the biomedical application, are rapidly extending into their niche. In the present work, triblock copolymer PEG-PLA-PEG synthesized and characterized by 1H -NMR and SEC can self-assemble into redox-responsive micelles in aqueous media with nanosized 33nm and 47nm. And the copolymers PEG2000-PLA3000-PEG2000 and PEG2000-PLA5000-PEG2000 present lower CMC with 0.034 and 0.022mg/mL, and higher DLC of 4.28% and 5.14% respectively, compared with that of diblock copolymer. Moreover, drug release from the micelles can be triggered and significantly accelerated in reductive environment. The low cytotoxicity of redox-responsive micelles was confirmed by MTT assay against NIH 3T3 cells. All of these results demonstrated that these polymeric micelles self-assembled from double-disulfide tethered block copolymers are promising carriers for the redox-responsive intracellular delivery of hydrophobic anticancer drugs.

PH-sensitive micelles self-assembled from polymer brush (PAE-g-cholesterol)-b-PEG-b-(PAE-g-cholesterol) for anticancer drug delivery and controlled release.

A novel amphiphilic pH-sensitive triblock polymer brush (poly(β-amino esters)-g-cholesterol)-b-poly(ethylene glycol)-b-(poly(β-amino esters)-g-cholesterol) ((PAE-g-Chol)-b-PEG-b-(PAE-g-Chol)) was designed and synthesized successfully through a three-step reaction, and their self-assembled polymeric micelles were used as hydrophobic anticancer drug delivery carriers to realize effectively controlled release. The critical micelle concentrations were 6.8 μg/mL, 12.6 μg/mL, 17.4 μg/mL, and 26.6 μg/mL at pH values of 7.4, 6.5, 6.0, and 5.0, respectively. The trend of critical micelle concentrations indicated that the polymer had high stability that could prolong the circulation time in the body. The hydrodynamic diameter and zeta potential of the polymeric micelles were influenced significantly by the pH values. As pH decreased from 7.4 to 5.0, the particle size and zeta potential increased from 205.4 nm to 285.7 nm and from +12.7 mV to +47.0 mV, respectively. The pKb of the polymer was confirmed to be approximately 6.5 by the acid–base titration method. The results showed that the polymer had sharp pH-sensitivity because of the protonation of the amino groups, resulting in transformation of the PAE segment from hydrophobic to hydrophilic. Doxorubicin-loaded polymeric micelles were prepared with a high loading content (20%) and entrapment efficiency (60%) using the dialysis method. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values. Furthermore, the drug release mechanism was also controlled by the pH values. The polymer had barely any cytotoxicity, whereas the doxorubicin-loaded system showed high toxicity for HepG2 cells as free drugs. All the results proved that the pH-sensitive triblock polymer brush and its self-assembled micelle might be a potential delivery carrier for anticancer drugs with sustained release.

Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

Many chemotherapeutics suffer from poor aqueous solubility and tissue selectivity. Distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) micelles are a promising formulation strategy for the delivery of hydrophobic anticancer drugs. However, storage and in vivo instability restrict their use. The aim of this study was to prepare mixed micelles, containing a novel polymer, lipoic acid-chitosan-poly(ethylene glycol) (LACPEG), and DSPE-PEG, to overcome these limitations and potentially increase cancer cell internalisation. Drug-loaded micelles were prepared with a model tyrosine kinase inhibitor and characterized for size, surface charge, stability, morphology, drug entrapment efficiency, cell viability (A549 and PC-9 cell lines), in vivo biodistribution, ex vivo tumor accumulation and cellular internalisation. Micelles of size 30–130nm with entrapment efficiencies of 46–81% were prepared. LACPEG/DSPE-PEG mixed micelles showed greater interaction with the drug (condensing to half their size following entrapment), greater stability, and a safer profile in vitro compared to DSPE-PEG micelles. LACPEG/DSPE-PEG and DSPE-PEG micelles had similar entrapment efficiencies and in vivo tumor accumulation levels, but LACPEG/DSPE-PEG micelles showed higher tumor cell internalisation. Collectively, these findings suggest that LACPEG/DSPE-PEG mixed micelles provide a promising platform for tumor delivery of hydrophobic drugs.

Co-delivery of hydrophilic and hydrophobic anticancer drugs using biocompatible pH-sensitive lipid-based nano-carriers for multidrug-resistant cancers

Simultaneous prolonged delivery of therapeutic gene, hydrophilic and hydrophobic anticancer drugs using biocompatible pH-sensitive LipoNiosome has been considered as a novel and promising method in order to treatment multi-drug resistant cancer.

Physico-Chemical Strategies to Enhance Stability and Drug Retention of Polymeric Micelles for Tumor-Targeted Drug Delivery.

Polymeric micelles (PM) have been extensively used for tumor-targeted delivery of hydrophobic anti-cancer drugs. The lipophilic core of PM is naturally suitable for loading hydrophobic drugs and the hydrophilic shell endows them with colloidal stability and stealth properties. Decades of research on PM have resulted in tremendous numbers of PM-forming amphiphilic polymers, and approximately a dozen micellar nanomedicines have entered the clinic. The first generation of PM can be considered solubilizers of hydrophobic drugs, with short circulation times resulting from poor micelle stability and unstable drug entrapment. To more optimally exploit the potential of PM for targeted drug delivery, several physical (e.g., π-π stacking, stereocomplexation, hydrogen bonding, host-guest complexation, and coordination interaction) and chemical (e.g., free radical polymerization, click chemistry, disulfide and hydrazone bonding) strategies have been developed to improve micelle stability and drug retention. In this review, the most promising physico-chemical approaches to enhance micelle stability and drug retention are described, and how these strategies have resulted in systems with promising therapeutic efficacy in animal models, paving the way for clinical translation, is summarized.

Anthracycline Drugs on Modified Surface of Quercetin-Loaded Polymer Nanoparticles: A Dual Drug Delivery Model for Cancer Treatment.

Polymer nanoparticles are vehicles used for delivery of hydrophobic anti-cancer drugs, like doxorubicin, paclitaxel or chemopreventors like quercetin (Q). The present study deals with the synthesis and characterisation of nano formulations (NFs) from Q loaded PLGA (poly lactic-co-glycolic acid) nano particles (NPs) by surface modification. The surface of Q-loaded (NPs) is modified by coating with biopolymers like bovine serum albumin (BSA) or histones (His). Conventional chemotherapeutic drugs adriamycin (ADR) and mitoxantrone (MTX) are bound to BSA and His respectively before being coated on Q-loaded NPs to nano formulate NF1 and NF2 respectively. The sizes of these NFs are in the range 400–500 nm as ascertained by SEM and DLS measurements. Encapsulation of Q in polymer NPs is confirmed from shifts in FT-IR, TGA and DSC traces of Q-loaded NPs compared to native PLGA and Q. Surface modification in NFs is evidenced by three distinct regions in their TEM images; the core, polymer capsule and the coated surface. Negative zeta potential of Q-loaded NPs shifted to positive potential on surface modification in NF1 and NF2. In vitro release of Q from the NFs lasted up to twenty days with an early burst release. NF2 is better formulation than NF1 as loading of MTX is 85% compared to 23% loading of ADR. Such NFs are expected to overcome multi-drug resistance (MDR) by reaching and treating the target cancerous cells by virtue of size, charge and retention.

CRGD-functionalized reduction-sensitive shell-sheddable biodegradable micelles mediate enhanced doxorubicin delivery to human glioma xenografts in vivo

Biodegradable micelles are one of the most studied systems for the delivery of hydrophobic anticancer drugs. Their therapeutic efficacy in vivo is, however, suboptimal, partly due to poor tumor cell uptake as well as slow intracellular drug release. Here, we show that cRGD-functionalized intracellularly shell-sheddable biodegradable PEG-SS-PCL micelles mediate enhanced doxorubicin (DOX) delivery to U87MG glioma xenografts in vivo, resulting in significantly improved tumor growth inhibition as compared to reduction-insensitive cRGD/PEG-PCL controls. cRGD/PEG-SS-PCL micelles revealed a small size of ca. 61nm, a decent DOX loading of 14.9wt%, and triggered drug release in a reductive environment (10mM glutathione). Flow cytometry, confocal microscopy, and MTT assays demonstrated that cRGD/PEG-SS-PCL micelles with a cRGD ligand density of 20% efficiently delivered and released DOX into αvβ3 integrin overexpressing U87MG cells. The in vivo pharmacokinetics studies displayed that DOX-loaded cRGD20/PEG-SS-PCL micelles had a prolonged elimination half-life time of 3.51h, which was comparable to that of cRGD20/PEG-PCL counterparts, indicating that disulfide bonds in the PEG-SS-PCL micelles are stable in the circulation. Notably, in vivo imaging and biodistribution studies in U87MG glioma xenografts showed that cRGD20/PEG-SS-PCL micelles led to efficient accumulation as well as fast drug release in the tumor. The therapeutic outcomes demonstrated that DOX-loaded cRGD20/PEG-SS-PCL micelles exhibited little side effects and superior tumor growth inhibition as compared to non-targeting PEG-SS-PCL and reduction-insensitive cRGD20/PEG-PCL counterparts. The reduction-sensitive shell-sheddable biodegradable micelles have appeared as a fascinating platform for targeted tumor chemotherapy.

Injectable micellar supramolecular hydrogel for delivery of hydrophobic anticancer drugs.

In this paper, an injectable micellar supramolecular hydrogel composed of α-cyclodextrin (α-CD) and monomethoxy poly(ethylene glycol)-b-poly(ε-caplactone) (MPEG5000-PCL5000) micelles was developed by a simple method for hydrophobic anticancer drug delivery. By mixing α-CD aqueous solution and MPEG5000-PCL5000 micelles, an injectable micellar supramolecular hydrogel could be formed under mild condition due to the inclusion complexation between α-CD and MPEG segment of MPEG5000-PCL5000 micelles. The resultant supramolecular hydrogel was thereafter characterized by X-ray diffraction (XRD) and Scanning electron microscopy (SEM). The effect of α-CD amount on the gelation time, mechanical strength and thixotropic property was studied by a rheometer. Payload of hydrophobic paclitaxel (PTX) to supramolecular hydrogel was achieved by encapsulation of PTX into MPEG5000-PCL5000 micelles prior mixing with α-CD aqueous solution. In vitro release study showed that the release behavior of PTX from hydrogel could be modulated by change the α-CD amount in hydrogel. Furthermore, such supramolecular hydrogel could enhance the biological activity of encapsulated PTX compared to free PTX, as indicated by in vitro cytotoxicity assay. All these results indicated that the developed micellar supramolecular hydrogel might be a promising injectable drug delivery system for anticancer therapy.

Pluronic stabilized Fe3O4 magnetic nanoparticles for intracellular delivery of curcumin

Water-dispersible Pluronic stabilized Fe3O4 magnetic nanoparticles were developed for intracellular delivery of hydrophobic anticancer drug.

Polymer nanocapsules for the intracellular delivery of hydrophobic and hydrophilic anticancer drugs

Polymer nanocapsules for the intracellular delivery of hydrophobic and hydrophilic anticancer drugs

An Acid-Triggered Degradable and Fluorescent Nanoscale Drug Delivery System with Enhanced Cytotoxicity to Cancer Cells.

To reduce side-effects of anticancer drugs, development of nanocarriers with precise biological functions is a critical requirement. In this study, the multifunctional nanoparticles combining imaging and therapy for tumor-targeted delivery of hydrophobic anticancer drugs were prepared via self-assembly of amphiphilic copolymers obtained using RAFT polymerization, specifically, acid-labile ortho ester and galactose. First, boron-dipyrromethene dye-conjugated chain transfer agent provides fluorescent imaging capability for diagnostic application. Second, nanoparticles were stable under physiological conditions but degraded in acidic tumor microenvironment, leading to enhanced anticancer efficacy. Third, the application of biocompatible glycopolymers efficiently increased the target-to-background ratio through carbohydrate-protein interactions. Data from cell viability, cellular internalization, flow cytometry, biodistribution and anticancer efficacy tests showed that the drug-loaded nanoparticles were capable of inhibiting cancer cell proliferation with significantly enhanced capacity. Our newly developed multifunctional nanoparticles may thus facilitate the development of effective drug delivery systems for application in diagnosis and therapy of cancer.

Redox-sensitive nanoparticles from amphiphilic cholesterol-based block copolymers for enhanced tumor intracellular release of doxorubicin

A novel amphiphilic cholesterol-based block copolymer comprised of a polymethacrylate bearing cholesterol block and a polyethylene glycol block with reducible disulfide bonds (PC5MA-SS-PEO) was synthesized and evaluated as a redox-sensitive nanoparticulate delivery system. The self-assembled PC5MA-SS-PEO nanoparticles (SS-NPs) encapsulated the anticancer drug doxorubicin (DOX) with high drug loading (18.2% w/w) and high encapsulation efficiency (94.9%). DOX-encapsulated PC5MA-SS-PEO self-assembled nanoparticles (DOX-encapsulated SS-NPs) showed excellent stability and exhibited a rapid DOX release in response to dithiothreitol reductive condition. Importantly, following internalization by lung cancer cells, the reducible DOX-encapsulated SS-NPs achieved higher cytotoxicity than the non-reducible thioester NPs whereas blank nanoparticles were non-cytotoxic. Furthermore, in vivo imaging studies in tumor-bearing severe combined immunodeficiency (SCID) mice showed that the nanoparticles preferentially accumulated in tumor tissue with remarkably reduced accumulation in the healthy non-target organs. The results indicated that the SS-NPs may be a promising platform for cancer-cell specific delivery of hydrophobic anticancer drugs. From the Clinical EditorThe use of nanocarriers for drug delivery against tumors has been under intense research. One problem of using carrier system is the drug release kinetics at tumor site. In this article, the authors continued their previous study in the development of an amphiphilic cholesterol-based block copolymer with redox-sensitive modification, so that the payload drug could be released in response to the microenvironment. The interesting results should provide a new direction for designing future novel nanocarrier systems.