Advanced biomaterials for cancer immunotherapy.

Immunotherapy, as a powerful strategy for cancer treatment, has achieved tremendous efficacy in clinical trials. Despite these advancements, there is much to do in terms of enhancing therapeutic benefits and decreasing the side effects of cancer immunotherapy. Advanced nanobiomaterials, including liposomes, polymers, and silica, play a vital role in the codelivery of drugs and immunomodulators. These nanobiomaterial-based delivery systems could effectively promote antitumor immune responses and simultaneously reduce toxic adverse effects. Furthermore, nanobiomaterials may also combine with each other or with traditional drugs via different mechanisms, thus giving rise to more accurate and efficient tumor treatment. Here, an overview of the latest advancement in these nanobiomaterials used for cancer immunotherapy is given, describing outstanding systems, including lipid-based nanoparticles, polymer-based scaffolds or micelles, inorganic nanosystems, and others.

Erythrocyte Membrane-Camouflaged IR780 and DTX Coloading Polymeric Nanoparticles for Imaging-Guided Cancer Photo-Chemo Combination Therapy.

Conventional systemic chemotherapy leads to poor therapeutic outcomes at moments in cancer therapy because the nontargeting anticancer drug release results in adverse effects and consequently drug resistance. The combination therapeutic strategy provides an alternative way to solve the conundrums. Herein, drug delivery systems with a rational design and tumor-targeting abilities become the ideal carriers for combinatorial therapy. IR780 iodide possesses near-infrared fluorescence intensity for fluorescence imaging (FI) and photothermal conversion for photoacoustic imaging (PAI), which also can be employed for tumor phototherapy (including photothermal therapy and photodynamic therapy). However, hydrophobicity and rapid elimination in vivo limit its biomedical applications. Furthermore, the hydrophobicity and high crystallization of IR780 result in poor drug-loading capacity and low stability. In this study, the high-pressure homogenization method was utilized for hydrophobic molecular IR780 and DTX coloading to construct IR780/DTX-PCEC nanoparticles which exhibit narrow size distribution and satisfactory drug-loading capacity. With further erythrocyte membrane [red blood cell (RBC)] camouflaging, the obtained IR780/DTX-PCEC@RBC nanoparticles present desired stability and prolonged circulation time in vivo. Additionally, the IR780/DTX-PCEC@RBC nanoparticles not only can be employed as a FI/PAI dual model imaging probe but also exhibit the property for phototherapy and chemotherapy of tumors. Based on the therapeutic outcome of combination therapy, the IR780/DTX-PCEC@RBC nanoparticles can serve as promising FI- and PAI-guided photo-chemo combination therapy agents for the future treatment of breast cancer.

Preparation and Properties of Nano-Hydroxyapatite/Gelatin/Poly(vinyl alcohol) Composite Membrane.

In this study, the bone-like composite membrane based on blends of gelatin (Gel), nano-hydroxyapatite (n-HA) and poly(vinyl alcohol) (PVA) was fabricated by solvent casting and evaporation methods. The effect of n-HA content and the ratio of Gel/PVA on the properties of the composite was investigated. The Gel/PVA and n-HA/Gel/PVA composite membranes were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), water contact angle measurement and scanning electron microscopy (SEM). The mechanical properties of the composites were determined by tensile tests. The as prepared composite membranes exhibited hydrophobility, the water contact angle of composite membrane was 126.6 when its mass ratio of n-HA/Gel/PVA was 10/50/40. The tensile strength of composite membranes was greatly increased due to the introduction of n-HA, and the tensile strength was increased to 74.92 MPa when the mass ratio of n-HA/Gel/PVA was 10/50/40. SEM observation indicated that n-HA was dispersed in the membranes and a sea-island structure was formed in the n-HA/Gel/PVA composite membranes, resulting in a significant increase in tensile strength. The as-prepared n-HA/Gel/PVA composite membranes may be applied in the field of bone tissue engineering.

Polysaccharide hydrogels: Functionalization, construction and served as scaffold for tissue engineering.

Polysaccharide hydrogels have been widely utilized in tissue engineering. They interact with the organismal environments, modulating the cargos release and realizing of long-term survival and activations of living cells. In this review, the potential strategies for modification of polysaccharides were introduced firstly. It is not only used to functionalize the polysaccharides for the consequent formation of hydrogels, but also used to introduce versatile side groups for the regulation of cell behavior. Then, techniques and underlying mechanisms in inducing the formation of hydrogels by polysaccharides or their derivatives are briefly summarized. Finally, the applications of polysaccharide hydrogels in vivo, mainly focus on the performance for alleviation of foreign-body response (FBR) and as cell scaffolds for tissue regeneration, are exemplified. In addition, the perspectives and challenges for further research are addressed. It aims to provide a comprehensive framework about the potentials and challenges that the polysaccharide hydrogels confronting in tissue engineering.

Tumor microenvironment-responsive Ag2S-PAsp(DOX)-cRGD nanoparticles-mediated photochemotherapy enhances the immune response to tumor therapy.

Chemotherapy drugs play important roles in clinical treatment, and most first-line regimens of cancer therapy contain chemotherapy drugs. In particular, some chemotherapeutic drugs can also produce ICD effect and enhance the immune response of the body. However, most chemotherapy drugs do not specifically target tumors or the complex tumor microenvironment, which renders their curative effect insufficient. Therefore, we constructed a tumor microenvironment-responsive drug delivery system (Ag2S-PAsp-cRGD) combined with doxorubicin (DOX) for tumor therapy. Firstly, Ag2S nanoparticles (NPs) were modified with polymer aspartic acid (PAsp) to construct the drug-loading platform. Then, an active targeting ligand (cRGD) was coupled through an amide reaction to enhance the functional targeting ability of the drug delivery system. In vivo imaging of the system showed that the nanoparticles accumulated in the tumor site, which facilitated the delivery of the chemotherapy drug DOX to the targeted tumor site. Furthermore, the photothermal effect of Ag2S NPs can effectively killed tumor cells, and also helped the release of DOX from nanoparticles into tumor tissue, thus enhancing the chemotherapeutic effect. Moreover, combined with the ICD effect jointly induced by photothermal therapy (PTT) and DOX, the treatment further activated the host immune response against tumors by enhancing the presentation of antigens and promoting the differentiation of T cells. This strategy of photo-chemo-immunotherapy showed excellent antitumor effect, not only eliminating the primary tumor but also preventing recurrence and inhibiting metastasis.

Preparation and release characteristic of quercetin loaded poly(lactic acid) ultrafine fibers.

In this study, poly(lactic acid) (PLA) ultrafine fibers have been prepared by electrospinning method using mix-solvent. The results showed that the variation of solvent ratio (N,N-dimethylformamide (DMF)/Dichloromethane (DCM)) could change the surface morphology of PLA nanofibers. By adjusting the solvent ratio, the quercetin release rate from the fiber membranes could be controlled. Furthermore, by adjusting the PLA concentration, the nanofibers without beads could be obtained. After addition of quercetin to polymer solution, the spindle-shaped beads on the fiber disappeared, but surface morphology of the fiber changed little with increase in quercetin dosage, and the release rate of quercetin increased with increase of quercetin dosage.

Preparation and characterization of poly(vinyl alcohol)/poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone)/nano-hydroxyapatite composite membranes for tissue engineering.

In this paper, the poly(vinyl alcohol)/poly(epsilon-caprolactone)-PEG-poly(epsilon-caprolactone)/nano-hydroxyapatite (PVA/PCEC/n-HA) composite membranes were prepared by solution casting and evaporation methods. The effect of n-HA content on the properties of the composite membranes was studied. The PVA/PCEC/n-HA composite membranes were analyzed by FTIR spectroscopy, X-ray diffraction, water content measurement, contact angle, mechanical test, scanning electron microscopy. The results showed that the surface roughness of the composite membranes increased with the increase of n-HA contents. The n-HA content had obvious influence on the swelling ratio, tensile strength and elongation rate of the composite membranes. With the increase of n-HA contents, the swelling ratio increased at first, and then decreased; tensile strength and elongation rate decreased gradually. The PVA/PCEC/n-HA composite membranes may be applied in the field of tissue engineering.

Intratumoral Injection of Norcantharidin-Loaded Poly(D,L-lactide)-b-Poly(ethylene glycol)-b-Poly(D,L-lactide) Thermosensitive Hydrogel for the Treatment of Primary Hepatocellular Carcinoma.

In this study we employed self-designed PDLLA-PEG-PDLLA (PLEL) thermosensitive hydrogel to blend with norcantharidin (NCTD), a hydrophilic chemotherapeutic drug possessing curative effect on primary hepatocellular carcinoma (HCC) and adverse effects, then utilized the composite in HCC interstitial chemotherapy. PLEL copolymer was synthesized by ring-opening polymerization, NCTD-loaded PLEL hydrogel was prepared in a simple and reasonable way. The addition of NCTD had no significant effect on the temperature-dependent rheological properties of PLEL hydrogel. The pH values of NCTD-loaded gel solutions (13 wt%) and free NCTD solutions with three drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL under different storage conditions met the pH requirement of small-volume injection. There was no significant difference among the drug release behaviors of NCTD-loaded gels with drug concentrations of 0.4 mg/mL, 0.8 mg/mL and 1.2 mg/mL, they fitted first-order dynamics, exhibited significantly slower drug release than free drug solutions and the release was mainly based on drug diffusion. Drug-loaded gel solution (13 wt%) could evenly distribute throughout tumor tissue before converting into gel after being intratumorally injected and was able to significantly prolong retention time of the drug in tumor compared to free drug solution. The sustained-release performance of NCTD-loaded gel (13 wt%) was confirmed from the perspective of pharmacodynamics in vitro. The in vivo evaluation demonstrated that intratumoral injection of NCTD-loaded PLEL gel (13 wt%) was capable of improving curative effect of the drug and reducing its toxicity.

Preparation of Adenosine-Loaded Electrospun Nanofibers and Their Application in Bone Regeneration.

The possibility of composite nanofibers being able to regenerate bone is an attractive proposition. Adenosine, which occurs naturally in humans, has been shown to promote the osteogenic differentiation of mesenchymal stem cells (MSCs) and osteoprogenitor cells. In this study, electrospun nanofibers of poly(3-hydroxybutyrate-co-3-hydroxybutyrate) (PHBV) doped with adenosine were demonstrated to exhibit excellent capacity for bone regeneration, after optimization of the electrospinning process. The biomechanical properties, hydrophilicity, biocompatibility, cellular performance of the nanofibers and adenosine release profile from the composite nanofibers were evaluated. The osteogenic capacity of the composite nanofibers in vitro and in vivo was systematically studied. Electrospun adenosine/PHBV nanofibers demonstrated excellent tissue biocompatibility. In addition, adenosine-loaded/PHBV electrospun nanofibers exhibited substantial bone regeneration capacity in vitro and in critical-sized rabbit cranial defects in vivo, which was greater than that of bone marrow MSC (BMSC)-loaded/PHBV electrospun nanofibers. Additionally, BMSCs/PHBV electrospun nanofibers required culture with BMSCs for a period of time prior to surgery, whereas the adenosine/PHBV electrospun nanofibers could be implanted directly. To date, there is seldom no studies have evaluated the capability of bone regeneration of electrospun nanofibers doped with adenosine. Using a simple fabrication process and with a structure similar to that of natural extracellular matrix (ECM), electrospun adenosine/PHBV nanofibers exhibited excellent biocompatibility and osteogenic capacity. In addition, adenosine is inexpensive, straightforward to obtain and store and so holds huge practical potential in bone tissue engineering applications.

Targeting Delivery of Lidocaine and Cisplatin by Nanogel Enhances Chemotherapy and Alleviates Metastasis.

Tumor growth inhibition and adverse effect reduction together with metastasis alleviation are still the challenges that need to be overcome in cancer chemotherapy. Combinational therapy provides an alternative solution for these challenges. Nanoparticles are the ideal carriers for combinational therapy due to their versatile drug loading capacities and versatile tumor-targeting strategies. In this study, a cRGDfk modified nanogel system has been utilized to coload lidocaine, a voltage-gated Na+ channels inhibitor, and cisplatin, a common anticancer drug to obtain a tumor-targeted dual drugs-loaded nanogel system. The introduction of lidocaine not only promotes the cisplatin-induced apoptosis in vitro and in vivo but also alleviates the metastasis of MDA-MB-231 breast cancer cells in the mouse model. Besides, the body weight loss caused by cisplatin has also been relieved, and higher dose with less body weight loss can be achieved, which indicated the adverse effect caused by cisplatin-mediated chemotherapy has been alleviated. Furthermore, the introduction of peptide segment-cRGDfk, which presents high affinity to αvß3 integrin, further increases the enrichment of drug-loaded nanogel in the tumor site. It favors the primary tumor growth inhibition. The results demonstrate the coloading of lidocaine and cisplatin by ligand-modified nanogels is a promising strategy for αvß3 integrin-overexpressing breast cancer combinational therapy.

α-Lipoic acid stabilized DTX/IR780 micelles for photoacoustic/fluorescence imaging guided photothermal therapy/chemotherapy of breast cancer.

Micellar nanoparticles have unique advantages as carriers for therapeutic or imaging agents, owing to their smaller size and better penetration of tumors. However, some agents, due to their physical or chemical properties, are difficult to load into micelles. IR780 is one of these agents, and is also a promising near-infrared dye for fluorescence imaging (FI)/photoacoustic imaging (PAI) and cancer photothermal therapy (PTT). Its hydrophobic and high crystallization structure results in limited bioavailability in vivo. It is difficult to load into micelles constructed from an amphiphilic block polymer with relatively low molecular weight. In this study, we use computer simulation and introduce another small biomolecule, α-lipoic acid, into the micelles constructed from a mPEG-PCL copolymer, to lower the energy of molecular interaction between MPEG-PCL and IR780, and expect to enhance the loading capacity of the micelles to IR780. The introduction of α-lipoic acid decreases the energy of molecular interaction between MEPG-PCL and IR780 from -46.18 kJ mol-1 to -196.52 kJ mol-1 and increases the loading capacity and stability of the mPEG-PCL micelles to IR780, which also maintains the loading capacity to DTX. We further construct DTX/IR780 co-loaded mPEG-PCL micelles for FI/PAI dual modal imaging guided PTT/chemotherapy of cancer. By FI and PAI evaluation in vitro and in vivo, we demonstrate that the DTX/IR780 co-loaded micelles can be used as FI and PAI probes. By further evaluating the therapeutic outcome of PTT/chemotherapy co-therapy of breast cancer, we demonstrate that the DTX/IR780 co-loaded mPEG-PCL micelles can serve as promising candidates for FI and PAI guided PTT/chemotherapy of breast cancer.

Oxygen-generating Hybrid Polymeric Nanoparticles with Encapsulated Doxorubicin and Chlorin e6 for Trimodal Imaging-Guided Combined Chemo-Photodynamic Therapy.

The combination of chemotherapy with photodynamic therapy (PDT) has attracted broad attention as it can overcome limitations of conventional chemo-treatment by using different modes of action. However, the efficacy of PDT to treat solid tumors is severely affected by hypoxia in tumors. Methods: In this study, we developed oxygen-generating theranostic nanoparticles (CDM NPs) by hierarchically assembling doxorubicin (DOX), chlorin e6 (Ce6) and colloidal manganese dioxide (MnO2) with poly (ε-caprolactone-co-lactide)-b-poly (ethylene glycol)-b-poly (ε-caprolactone-co-lactide) for treating breast cancer. The in vitro and in vivo antitumor efficacy and imaging performance were investigated. Results: The theranostic nanoparticles showed high stability and biocompatibility both in vitro and in vivo. MnO2 within the nanoparticles could trigger decomposition of excessive endogenous H2O2 in the tumor microenvironment to generate oxygen in-situ to relieve tumor hypoxia. With enhanced oxygen generation, the PDT effect was significantly improved under laser-irradiation. More importantly, this effect together with that of DOX was able to dramatically promote the combined chemotherapy-PDT efficacy of CDM NPs in an MCF-7 tumor-bearing mouse model. Furthermore, the real-time tumor accumulation of the nanocomposites could be monitored by fluorescence imaging, photoacoustic (PA) imaging and magnetic resonance imaging (MRI). Conclusion: The designed CDM NPs are expected to provide an alternative way of improving antitumor efficacy by combined chemo-PDT further enhanced by oxygen generation, and would have broad applications in cancer theranostics.

Preparation of Hydrogel Based on Poly(ester amine) (PEA) for Bilirubin Removal.

Hyperbilirubinemia, caused by the disorders in bilirubin metabolism, could result in neurotoxicity, permanent brain damage and even death. As one of effective bilirubin removal technologies from blood, hemoperfusion had attracted much attention. However, the development of bilirubin adsorbents used in hemoperfusion with excellent adsorption capacity and hemocompatibility still faced great challenges. In this work, the cationic hydrogel was prepared by the photo-initiated polymerization of biodegradable poly(ester amine) (PEA) based on PLLA and low molecular weight PEI1800. The PEA hydrogel had favorable swelling behavior and bilirubin adsorption capacity, and the bilirubin adsorption amount could reach up to 374.43 mg/g. The effects of pH value, ionic strength and human serum albumin (HSA) were also studied. Besides, the results of hemolytic test indicated that PEA hydrogel had favorable hemocompatibility. Based on these results, the prepared PEA hydrogel would be quite hopeful as an effective adsorbent for bilirubin removal from blood.

A novel botryoidal aramid fiber reinforcement of a PMMA resin for a restorative biomaterial.

Poly(methyl methacrylate) (PMMA) resin is widely used as a prosthetic and restorative biomaterial, such as in bone cement, denture base resin, etc. The flexural and compressive strength of a PMMA resin is of great concern and many approaches have been made to improve the flexural resistance and compressive strength of PMMA. To strengthen PMMA via high-performance (HP) fibers is a feasible way; however, the HP fibers are not very satisfactory in practice, with a complex handling process and esthetic concerns. The aim of this study is to investigate the preparation of a novel botryoidal PMMA microsphere-grafted aramid fiber system, which has never been reported before, and the flexural and compression behavior of the PMMA/aramid composite, and evaluate the cytotoxic effects of the PMMA/aramid composite. As a result, the addition of a microsphere-grafted aramid fiber to an acrylic resin, with the esthetic problem of the aramid fiber minimized, simultaneously improves the mechanical properties and the safety of the PMMA/aramid composite in vitro is proven acceptable, suggesting that the novel composite has great potential in the field of restorative materials in clinical applications where high mechanical properties are required such as hard tissue repairing.

Recent Progress in Functional Micellar Carriers with Intrinsic Therapeutic Activities for Anticancer Drug Delivery.

Polymeric micelles have presented superior delivery properties for poorly water-soluble chemotherapeutic agents. However, it remains discouraging that there may be some additional short or long-term toxicities caused by the metabolites of high quantities of carriers. If carriers had simultaneous therapeutic effects with the drug, these issues would not be a concern. For this, carriers not only simply act as drug carriers, but also exert an intrinsic therapeutic effect as a therapeutic agent. The functional micellar carriers would be beneficial to maximize the anticancer effect, overcome the drug resistance and reduce the systemic toxicity. In this review, we aim to summarize the recent progress on the development of functional micellar carriers with intrinsic anticancer activities for the delivery of anticancer drugs. This review focuses on the design strategies, properties of carriers and the drug loading behavior. In addition, the combinational therapeutic effects between carriers and chemotherapeutic agents are also discussed.

A Novel MPEG-PDLLA-PLL Copolymer for Docetaxel Delivery in Breast Cancer Therapy.

Satisfactory drug loading capacity and stability are the two main factors that determine the anti-cancer performance. In general, the stability of the micelles is reduced when the drug loading (DL) is increased. Therefore, it was a challenge to have high drug loading capacity and good stability. In this study, we introduced a hydrophilic poly (L-Lysine) (PLL) segment with different molecular-weights into the monomethoxy poly (ethylene glycol)-poly (D, L-lactide) (MPEG-PDLLA) block copolymer to obtain a series of novel triblock MPEG-PDLLA-PLL copolymers. We found that the micelles formed by a specific MPEG2k-PDLLA4k-PLL1k copolymer could encapsulate docetaxel (DTX) with a satisfactory loading capacity of up to 20% (w/w) via the thin film hydration method, while the stability of drug loaded micellar formulation was still as good as that of micelles formed by MPEG2k-PDLLA1.7k with drug loading of 5% (w/w). The results from computer simulation study showed that compared with MPEG2k-PDLLA1.7k, the molecular chain of MPEG2k-PDLLA4k-PLL1k could form a more compact funnel-shaped structure when interacted with DTX. This structure favored keeping DTX encapsulated in the copolymer molecules, which improved the DL and stability of the nano-formulations. The in vitro and in vivo evaluation showed that the DTX loaded MPEG2k-PDLLA4k-PLL1k (DTX/MPEG2k-PDLLA4k-PLL1k) micelles exhibited more efficiency in tumor cell growth inhibition. In conclusion, the MPEG2k-PDLLA4k-PLL1k micelles were much more suitable than MPEG2k-PDLLA1.7k for DTX delivery, and then the novel nano-formulations showed better anti-tumor efficacy in breast cancer therapy.

Novel Approach of Using Near-Infrared Responsive PEGylated Gold Nanorod Coated Poly(l-lactide) Microneedles to Enhance the Antitumor Efficiency of Docetaxel-Loaded MPEG-PDLLA Micelles for Treating an A431 Tumor.

The combination of chemotherapy and photothermal therapy (PTT) plays a significant role in synergistic tumor therapy. However, a high dosage of chemotherapy drugs or photothermal agents may cause series side effects. To overcome these challenges, we designed a near-infrared (NIR) responsive PEGylated gold nanorod (GNR-PEG) coated poly(l-lactide) microneedle (PLLA MN) system (GNR-PEG@MN) to enhance antitumor efficiency of docetaxel-loaded MPEG-PDLLA (MPEG-PDLLA-DTX) micelles for treating an A431 tumor. The as-made GNR-PEG@MNs contained only 31.83 ± 1.22 µg of GNR-PEG per patch and exhibited excellent heating efficacy both in vitro and in vivo. Meanwhile, GNR-PEG@MN with the height of 480 µm had good skin insertion ability and was harmless to the skin. On the other hand, GNR-PEG@MN had good heating transfer ability in vivo, and the tumor sites could reach 50 °C within 5 min. In comparison with chemotherapy and PTT alone, the combination of low dosage MPEG-PDLLA-DTX micelles (5 mg/kg) and GNR-PEG@MNs completely eradicated the A431 tumor without recurrence in vivo, demonstrating a remarkable synergetic effect. Hence, GNR-PEG@MN could be a promising carrier to enhance the antitumor effect of MPEG-PDLLA-DTX micelles for treating superficial tumors and is expected to have a great potential in clinical translation for human epidermoid cancer therapy.

Targeting Therapy of Neuropilin-1 Receptors Overexpressed Breast Cancer by Paclitaxel-Loaded CK3-Conjugated Polymeric Micelles.

Chemotherapy for breast cancer is significantly restricted by the tumor's physio-pathological complexity. Here we have constructed a targeted nano-system based on PEGylated poly (D, L-lactide) (PEG-PDLLA) using a novel ligand, CLKADKAKC (CK3) peptide, for active targeting to Neuropilin-1-rich breast cancer cells. CK3 increased the cellular uptake of micelles 4.7-fold compared with the free drug and nearly 2.2-fold compared with the unmodified micelles (PM), respectively. Furthermore, in vivo imaging revealed that CK3-modified micelles (CK3-PM) had excellent specific tumor cells targeting and the drug accumulation was also enhanced. When paclitaxel (PTX) was loaded into micelles, CK3-PM-PTX induced the strongest inhibition and apoptosis against MDA-MB-231 cells in vitro and in vivo. These results demonstrated that CK3-modified PEG-PDLLA micelles developed in this study could be a potential targeted vehicle for enhancing the chemotherapy of breast cancers.

An efficient injectable formulation with block copolymer micelles for hydrophobic antitumor candidate-pyridazinone derivatives.

AIM: To make delivery improvements via delivery systems for 6-(4-morpholino-3-(trifluoromethyl)phenyl)pyridazin-3(2H)-one (DZO) - a model compound of hydrophobic antitumor candidate pyridazinone derivatives. MATERIALS & METHODS: Methoxy poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PDLLA) micelle was employed as a vector, and DZO was encapsulated in. The DZO-loaded micelles were characterized in detail and its cytotoxicity, maximum tolerated dose (MTD) and pharmacokinetic experiments were done. In vivo anticancer activity was studied through a subcutaneous 4T1 tumor model. RESULTS: Compared with free DZO, the DZO-loaded micelles possessed a sustained release property, an improved MTD, better pharmacokinetic parameters and an enhanced antitumor activity for subcutaneous 4T1 model in vivo. CONCLUSION: An effective injectable delivery system for DZO was developed successfully.

Anti-tumor activity and safety evaluation of fisetin-loaded methoxy poly(ethylene glycol)-poly(epsilon-caprolactone) nanoparticles.

Fisetin (3,3',4',7-tetrahydroxyflavone) is a potential anti-tumor agent but poor water solubility hinders its application and complicates direct parenteral administration. Nanoparticle encapsulation is an efficient way to enhance the solubility of some hydrophobic drugs. In this study, methoxy poly(ethylene glycol)-polycaprolactone (MPEG-PCL) nanoparticles were successfully prepared for fisetin delivery in vitro and in vivo. Narrow distribution fisetin-loaded MPEG-PCL NPs (aproximately100 nm) were obtained via emulsification (O/W) and displayed a sustained release behavior in vitro. Moreover, hemolysis and cell cytotoxicity testing showed that MPEG-PCL is biocompatible and safe for intravenous injection. Most importantly, NPs encapsulation enhanced the anti-cancer activity of fisetin as shown in a subcutaneous LL/2 tumor model, and reduced the hepatotoxicity of fisetin. Therefore, our data demonstrate that fisetin-loaded MPEG-PCL NPs have potential application in cancer chemotherapy.