Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy.

Despite decades of laboratory and clinical trials, breast cancer remains the main cause of cancer-related disease burden in women. Considering the metabolism destruction effect of metformin (Met) and cancer cell starvation induced by glucose oxidase (GOx), after their efficient delivery to tumor sites, GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ. Herein, a pH-responsive epigallocatechin gallate (EGCG)-conjugated low-molecular-weight chitosan (LC-EGCG, LE) nanoparticle (Met-GOx/Fe@LE NPs) was constructed. The coordination between iron ions (Fe3+) and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction. Met-GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability. Moreover, this pH-responsive nanoplatform presents controllable drug release behavior. An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug. The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation. This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

MXene-based polysaccharide aerogel with multifunctional enduring antimicrobial effects for infected wound healing.

Wound infection is a predominant etiological factor contributing to delayed wound healing in open wounds. Hence, it holds paramount clinical significance to devise wound dressings endowed with superior antibacterial properties. In this study, a Schiff base-crosslinked aerogel comprising sodium alginate oxide (OSA), carboxymethyl chitosan (CMCS), and Nb2C@Ag/PDA (NAP) was developed. The resultant OSA/CMCS-Nb2C@Ag/PDA (OC/NAP) composite aerogel exhibited commendable attributes including exceptional swelling characteristics, porosity, biocompatibility, and sustained antimicrobial efficacy. In vitro antimicrobial assays unequivocally demonstrated that the OC/NAP composite aerogel maintained nearly 100 % inhibition of Staphylococcus aureus and Escherichia coli under an 808 nm laser even after 25 h. Crucially, the outcomes of in vivo infected wound healing experiments demonstrated that the wound healing rate of the OC/NAP composite aerogel group reached approximately 100 % within a span of 14 days, which was significantly greater than that of the blank control group. In vitro and in vivo hemostatic experiments also revealed that the composite aerogel had excellent hemostatic properties. The results of this study demonstrate the remarkable potential of OC/NAP aerogel as a multifunctional clinical wound dressing, especially for infected wounds.

Polysaccharides as a promising platform for the treatment of spinal cord injury: A review.

Spinal cord injury is incurable and often results in irreversible damage to motor function and autonomic sensory abilities. To enhance the effectiveness of therapeutic substances such as cells, growth factors, drugs, and nucleic acids for treating spinal cord injuries, as well as to reduce the toxic side effects of chemical reagents, polysaccharides have been gained attention due to their immunomodulatory properties and the biocompatibility and biodegradability of polysaccharide scaffolds. Polysaccharides hold potential as drug delivery systems in treating spinal cord injuries. This article aims to present an extensive evaluation of the potential applications of polysaccharide materials in scaffold construction, drug delivery, and immunomodulation over the past five years so that offering new directions and opportunities for the treatment of spinal cord injuries.

The potential of mRNA vaccines in cancer nanomedicine and immunotherapy.

Owing to their outstanding performance against COVID-19, mRNA vaccines have brought great hope for combating various incurable diseases, including cancer. Differences in the encoded proteins result in different molecular and cellular mechanisms of mRNA vaccines. With the rapid development of nanotechnology and molecular medicine, personalized antigen-encoding mRNA vaccines that enhance antigen presentation can trigger effective immune responses and prevent off-target toxicities. Herein, we review new insights into the influence of encoded antigens, cytokines, and other functional proteins on the mechanisms of mRNA vaccines. We also highlight the importance of delivery systems and chemical modifications for mRNA translation efficiency, stability, and targeting, and we discuss the potential problems and application prospects of mRNA vaccines as versatile tools for combating cancer.

Metal-organic framework-based photodynamic combined immunotherapy against the distant development of triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive, metastatic and apparently drug-resistant subtype of breast cancer with a higher immune response compared to other types of breast cancer. Photodynamic therapy (PDT) has been gaining popularity for its non-invasive nature, minimal side effects, and spatiotemporally controlled benifits. The use of metal-organic frameworks (MOFs) loaded with programmed death-ligand 1 inhibitors (iPD-L1) offers the possibility of combining PDT with immunotherapy. METHOD: Here, we construct PCN-224, a MOFs with good biocompatibility and biodegradability for the delivery of the PD-L1 small molecule inhibitor BMS-202 to achieve a synergistic anti-tumor strategy of PDT and immunotherapy. Hyaluronic acid (HA) modified PEG (HA-PEG) was synthesized for the outer layer modification of the nanocomplex, which prolongs its systemic circulation time. RESULTS: In vitro cellular experiments show that the nanocomplexes irradiated by 660 nm laser has a strong ability to produce singlet oxygen, which effectively induce PDT. PDT with strong immunogenicity leads to tumor necrosis and apoptosis, and induces immunogenic cell death, which causes tumor cells to release danger associated molecular patterns. In combination with iPD-L1, the combination therapy stimulates dendritic cell maturation, promotes T-cell activation and intratumoral infiltration, and reshapes the tumor immune microenvironment to achieve tumor growth inhibition and anti-distant tumor progression. CONCLUSIONS: MOFs-based nano-systems as a platform for combination therapy offer a potentially effective strategy for the treatment of TNBC with high metastatic rates.

Case Report: Successful Use of BRAF/MEK Inhibitors in Aggressive BRAF-mutant Craniopharyngioma.

BACKGROUND: Although a benign intracranial tumor, craniopharyngioma treatment has always been considered a challenging clinical problem. Recently, BRAF V600E mutation in the pathogenesis of papillary craniopharyngioma (PCP) has been further revealed. Thus, BRAF inhibitors (BRAFi) serve as an applicable treatment for patients with PCP. METHODS: Two patients with recurrent PCP were treated with combined BRAFi dabrafenib (150 mg, orally twice daily) and MEK inhibitors (MEKi) trametinib (2 mg, orally twice daily). A follow-up exceeding 2 years was conducted. We meticulously scrutinized the treatment's safety and efficacy profiles by delving into existing literature. RESULTS: One patient harboring a solid tumor achieved a complete tumor response devoid of any adverse events and encountered no recurrence over 2 years subsequent to discontinuation. Moreover, within a mere month of commencing targeted therapy, the tumor demonstrated observable shrinkage. This finding substantiates the considerable potential inherent in targeted therapy for PCP cases marked by the somatic BRAF V600E mutation. CONCLUSIONS: Under specific conditions, individuals diagnosed with PCP can attain a complete tumor response following combined treatment with BRAFi/MEKi.

Lipid-Polymer Hybrid Nanoparticles with Both PD-L1 Knockdown and Mild Photothermal Effect for Tumor Photothermal Immunotherapy.

In developing countries, the incidence of colorectal cancer (CRC) is on the rise. The combination of programmed cell death ligand-1 (PD-L1) siRNA (siPD-L1) and mild photothermal therapy (PTT) is a promising strategy for CRC treatment. In this study, dopamine-modified polyethylenimine (PEI) was prepared to fabricate an IR780 and siPD-L1 codelivery lipid-polymer hybrid nanoparticle (lip@PSD-siP) for the photothermal immunotherapy of CRC. The modification of dopamine can significantly reduce the cytotoxicity of PEI. lip@PSD-siP can be effectively taken up by CT26 cells and successfully escaped from lysosomes after entering the cells for 4 h. After CT26 cells were transfected with lip@PSD-siP, the PD-L1 positive cell rate decreased by 82.4%, and its PD-L1 knockdown effect was significantly stronger than the positive control Lipo3000-siP. In vivo studies showed that lip@PSD-siP-mediated mild PTT and efficient PD-L1 knockdown exhibited primary and distal tumor inhibition, metastasis delay, and rechallenged tumor inhibition. The treatment with lip@PSD-siP significantly promoted the maturation of dendritic cells in lymph nodes. The amount of T cell infiltration in the tumor tissues increased significantly, and the frequency of CD8+ T cells and CD4+ T cells was significantly higher than that of other groups. The percentage of immunosuppressive regulatory cells (Tregs) in the tumor tissue on the treatment side decreased by 88% compared to the PBS group, and the proportion of CD8+CD69+ T cells in the distal tumor tissue was 2.8 times that of the PBS group. The memory T cells of mice in the long-term antitumor model were analyzed. The results showed that after treatment with lip@PSD-siP, the frequency of effector memory T cells (Tem cells) significantly increased, suggesting the formation of immune memory.

Polyphenol-Based Nanosystems for Next-Generation Cancer Therapy: Multifunctionality, Design, and Challenges.

With the continuous updating of cancer treatment methods and the rapid development of precision medicine in recent years, there are higher demands for advanced and versatile drug delivery systems. Scientists are committed to create greener and more effective nanomedicines where the carrier is no longer limited to a single function of drug delivery. Polyphenols, which can act as both active ingredients and fundamental building blocks, are being explored as potential multifunctional carriers that are efficient and safe for design purposes. Due to their intrinsic anticancer activity, phenolic compounds have shown surprising expressiveness in ablation of tumor cells, overcoming cancer multidrug resistance (MDR), and enhancing immunotherapeutic efficacy. This review provides an overview of recent advances in the design, synthesis, and application of versatile polyphenol-based nanosystems for cancer therapy in various modes. Moreover, the merits of polyphenols and the challenges for their clinical translation are also discussed, and it is pointed out that the novel polyphenol delivery system requires further optimization and validation.

Single-cell RNA sequencing highlights intratumor heterogeneity and intercellular network featured in adamantinomatous craniopharyngioma.

Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.

Engineering MMP-2 Activated Nanoparticles Carrying B7-H3 Bispecific Antibodies for Ferroptosis-Enhanced Glioblastoma Immunotherapy.

Administration of bispecific antibodies (biAbs) in tumor therapy is limited by their short half-life and off-target toxicity. Optimized strategies or targets are needed to overcome these barriers. B7-H3 (CD276), a member of the B7 superfamily, is associated with poor survival in glioblastoma (GBM) patients. Moreover, a dimer of EGCG (dEGCG) synthesized in this work enhanced the IFN-γ-induced ferroptosis of tumor cells in vitro and in vivo. Herein, we prepared recombinant anti-B7-H3×CD3 biAbs and constructed MMP-2-sensitive S-biAb/dEGCG@NPs to offer a combination treatment strategy for efficient and systemic GBM elimination. Given their GBM targeted delivery and tumor microenvironment responsiveness, S-biAb/dEGCG@NPs displayed enhanced intracranial accumulation, 4.1-, 9.5-, and 12.3-fold higher than that of biAb/dEGCG@NPs, biAb/dEGCG complexes, and free biAbs, respectively. Furthermore, 50% of GBM-bearing mice in the S-biAb/dEGCG@NP group survived longer than 56 days. Overall, S-biAb/dEGCG@NPs can induce GBM elimination by boosting the ferroptosis effect and enhancing immune checkpoint blockade (ICB) immunotherapy and may be successful antibody nanocarriers for enhanced cancer therapy.

Roles of MXenes in biomedical applications: recent developments and prospects.

....With the development of nanomedical technology, the application of various novel nanomaterials in the biomedical field has been greatly developed in recent years. MXenes, which are new inorganic nanomaterials with ultrathin atomic thickness, consist of layered transition metal carbides and nitrides or carbonitrides and have the general structural formula Mn+1XnTx (n = 1-3). Based on the unique structural features of MXenes, such as ultrathin atomic thickness and high specific surface area, and their excellent physicochemical properties, such as high photothermal conversion efficiency and antibacterial properties, MXenes have been widely applied in the biomedical field. This review systematically summarizes the application of MXene-based materials in biomedicine. The first section is a brief summary of their synthesis methods and surface modification strategies, which is followed by a focused overview and analysis of MXenes applications in biosensors, diagnosis, therapy, antibacterial agents, and implants, among other areas. We also review two popular research areas: wearable devices and immunotherapy. Finally, the difficulties and research progress in the clinical translation of MXene-based materials in biomedical applications are briefly discussed.

Boosting ferroptosis and microtubule inhibition for antitumor therapy via a carrier-free supermolecule nanoreactor.

Traditional microtubule inhibitors fail to significantly enhance the effect of colorectal cancer; hence, new and efficient strategies are necessary. In this study, a supramolecular nanoreactor (DOC@TA-Fe3+) based on tannic acid (TA), iron ion (Fe3+), and docetaxel (DOC) with microtubule inhibition, reactive oxygen species (ROS) generation, and glutathione peroxidase 4 (GPX4) inhibition, is prepared for ferroptosis/apoptosis treatment. After internalization by CT26 cells, the DOC@TA-Fe3+ nanoreactor escapes from the lysosomes to release payloads. The subsequent Fe3+/Fe2+ conversion mediated by TA reducibility can trigger the Fenton reaction to enhance the ROS concentration. Additionally, Fe3+ can consume glutathione to repress the activity of GPX4 to induce ferroptosis. Meanwhile, the released DOC controls microtubule dynamics to activate the apoptosis pathway. The superior in vivo antitumor efficacy of DOC@TA-Fe3+ nanoreactor in terms of tumor growth inhibition and improved survival is verified in CT26 tumor-bearing mouse model. Therefore, the nanoreactor can act as an effective apoptosis and ferroptosis inducer for application in colorectal cancer therapy.

Polydopamine-coated i-motif DNA/Gold nanoplatforms for synergistic photothermal-chemotherapy.

The combination of photothermal therapy with chemotherapy has gradually developed into promising cancer therapy. Here, a synergistic photothermal-chemotherapy nanoplatform based on polydopamine (PDA)-coated gold nanoparticles (AuNPs) were facilely achieved via the in situ polymerization of dopamine (DA) on the surface of AuNPs. This nanoplatform exhibited augmented photothermal conversion efficiency and enhanced colloidal stability in comparison with uncoated PDA shell AuNPs. The i-motif DNA nanostructure was assembled on PDA-coated AuNPs, which could be transformed into a C-quadruplex structure under an acidic environment, showing a characteristic pH response. The PDA shell served as a linker between the AuNPs and the i-motif DNA nanostructure. To enhance the specific cellular uptake, the AS1411 aptamer was introduced to the DNA nanostructure employed as a targeting ligand. In addition, Dox-loaded NPs (DAu@PDA-AS141) showed the pH/photothermal-responsive release of Dox. The photothermal effect of DAu@PDA-AS141 elicited excellent photothermal performance and efficient cancer cell inhibition under 808 nm near-infrared (NIR) irradiation. Overall, these results demonstrate that the DAu@PDA-AS141 nanoplatform shows great potential in synergistic photothermal-chemotherapy.

Multifunctional gold nanorods in low-temperature photothermal interactions for combined tumor starvation and RNA interference therapy.

Collateral damage to healthy tissue, uneven heat distribution, inflammatory diseases, and tumor metastasis induction hinder the translation of high-temperature photothermal therapy (PTT) from bench to practical clinical applications. In this report, a multifunctional gold nanorod (GNR)-based nanosystem was designed by attaching siRNA against B7-H3 (B7-H3si), glucose oxidase (GOx), and hyaluronic acid (HA) for efficient low-temperature PTT. Herein, GOx can not only exhaust glucose to induce starvation therapy but also reduce the heat shock protein (HSP), realizing the ablation of tumors without damage to healthy tissues. Evidence shows that B7-H3, a type I transmembrane glycoprotein molecule, plays essential roles in growth, metastasis, and drug resistance. By initiating the downregulation of B7-H3 by siRNA, siRNA-GOx/GNR@HA NPs may promote the effectiveness of treatment. By targeting cluster of differentiation 44 (CD44) and depleting B7-H3 and HSPs sequentially, siRNA-GOx/GNR@HA NPs showed 12.9-fold higher lung distribution than siRNA-GOx/GNR NPs. Furthermore, 50% of A549-bearing mice in the siRNA-GOx/GNR NPs group survived over 50 days. Overall, this low-temperature phototherapeutic nanosystem provides an appropriate strategy for eliminating cancer with high treatment effectiveness and minimal systemic toxicity. STATEMENT OF SIGNIFICANCE: To realize efficient tumor ablation under mild low-temperature (42-45 â„ƒ) and RNA interference simultaneously, here we developed a multifunctional gold nanorod (GNR)-based nanosystem (siRNA-GOx/GNR@HA NPs). This nanoplatform can significantly inhibit tumor cell proliferation and induce cell apoptosis by downregulation of HSP90α, HSP70, B7-H3, p-AKT, and p-ERK and upregulation of cleaved caspase-9 at mild low-temperature due to its superior tumor homing ability and the combined effect of photothermal effect, glucose deprivation-initiated tumor starvation, and B7-H3 gene silence effect. It is believed that this multifunctional low-temperature photothermal nanosystem with efficient and specific anticancer properties, shows a potential application in clinical tumor treatment.

Expression and clinical significance of VISTA, B7-H3, and PD-L1 in glioma.

Immune checkpoint (IC) therapy has led to a breakthrough in cancer treatment. However, the interaction of ICs is controversial in glioma. We detected features of ICs using transcriptome data and a multicolor immunofluorescence assay. We discovered that B7-H3 increased with grade and age and predicted worse overall survival (OS) at the transcriptional and proteomic levels. VISTA and PD-L1 were associated with OS and grade at the RNA level. At the protein level, VISTA was primarily expressed in tumor cells and TAMs. B7-H3 and VISTA were positively correlated with PD-L1. There was a strong correlation between PD-L1 and CD3 and between VISTA and IBA-1. PD-L1 was coexpressed with T cells. VISTA was coexpressed with TAMs. In T cells, we found a strong correlation in ICs, which worsened in TAMs and tumor cells. In conclusion, B7-H3 is a vital prognostic target for immunotherapy. We provided a potential mechanism for the immunosuppressive microenvironment in glioma.

Functionalized chitosan as a promising platform for cancer immunotherapy: A review.

Immunotherapy is an emerging treatment option for use following traditional cancer treatments (surgical resection, radiotherapy and chemotherapy). Due to the complexity of the tumor environment, a single immunotherapy drug cannot readily reach the target site and frequently causes adverse reactions. Chitosan has been used in this emerging field because of its biodegradable, biocompatible, nonimmunogenic and nontoxic properties. Chitosan has been used as a carrier of immunotherapeutic agents to improve bioavailability, regulate the immune system and enhance antitumor response. The easily modified structure of chitosan allows for the construction of many different delivery vectors for better application in immunotherapy. Here, we review the recent applications of chitosan and its derivatives as delivery vectors in cancer immunotherapy, as well as discuss limitations and clarify current trends and future directions. In conclusion, chitosan has a promising future as a delivery material in immunotherapy.

Development and evaluation of a novel biodegradable implants with excellent inflammatory response suppression effect by hot-melt extrusion.

PURPOSE: Dexamethasone (Dex) is a widely used drug for the treatment of inflammatory and autoimmune conditions, however, long-term systemic use of Dex is associated with serious adverse effects. The objective of the present study was to develop an implantable device to avoid side effects and realize a controlled release of Dex at the implant site. METHODS: Hydrophobic Dex was incorporated into biodegradable polyesters derived from PCL and Pluronic® L64 (PCL-Pluronic L64-PCL, PCLC) by hot-melt extrusion (HME) method to prepare Dex/PCLC implantable devices. Drug loading and encapsulation efficiency, a series of physicochemical properties, and in vivo features of the implants were studied. RESULTS: The maximum value of the drug loading and encapsulation efficiency for the Dex/PCLC implants were up to 47% and 94%, respectively. Incorporation of Dex resulted in accelerated crystallization of PCLC, decreased the wettability, increased contact angles and viscosity, and accelerated Dex release rate and degradation rate from the implants in vivo. Moreover, Dex/PCLC implants showed excellent biocompatibility. Furthermore, the inflammatory response to the Dex/PCLC implants was less severe than that to the positive control group. CONCLUSION: All these results suggested that Dex/PCLC implants might be a safe and controlled local drug delivery system with excellent inflammatory response suppression effect.

Chitosan coated pH-responsive metal-polyphenol delivery platform for melanoma chemotherapy.

The safe and effective drug delivery system is important for cancer therapy. Here in, we first constructed a delivery system Cabazitaxel(Cab)@MPN/CS between metal-polyphenol (MPN) and chitosan (CS) to deliver Cab for melanoma therapy. The preparation process is simple, green, and controllable. After introducing CS coating, the drug loading was improved from 7.56 % to 9.28 %. Cab@MPN/CS NPs released Cab continuously under acid tumor microenvironment. The zeta potential of Cab@MPN/CS NPs could be controlled by changing the ratio of Cab@MPN and CS solutions. The positively charged Cab@MPN/CS accelerate B16F10 cell internalization. After internalized, Cab@MPN/CS NPs could escape from lysosomes via the proton sponge effect. The permeability of CS promotes the penetration of Cab@MPN/CS to the deeper B16F10 tumor spheroids. In vivo results showed that Cab@MPN/CS NPs have a longer retention time in tumor tissues and significantly inhibit tumor growth by up-regulating TUNEL expression and down-regulating KI67 and CD31 expression. Thus, this delivery system provides a promising strategy for the tumor therapy in clinic.

A Tumor-Specific Ferric-Coordinated Epigallocatechin-3-gallate cascade nanoreactor for glioblastoma therapy.

Introduction: Numerous options for treatment of glioblastoma have been explored; however, single-drug therapies and poor targeting have failed to provide effective drugs. Chemotherapy has significant antitumor effect, but the efficacy of single-drug therapies in the clinic is limited over a long period of time. Thus, novel therapeutic approaches are necessary to address these critical issues. Objectives: The present study, we investigated a tumor-specific metal-tea polyphenol-based cascade nanoreactor for chemodynamic therapy-enhanced chemotherapy. Methods: HA-EGCG was synthesized for the first time by introducing epigallocatechin-3-gallate (EGCG) into the skeleton of hyaluronic acid (HA) with reducible disulfide bonds. A rapid and green method was developed to fabricate the metal-tea polyphenol networks (MTP) with an HA-EGCG coating (DOX@MTP/HA-EGCG) based on Fe3+ and EGCG for targeted delivery of doxorubicin hydrochloride (DOX). GL261 cells were used to evaluate the antitumor efficacy of the DOX@MTP/HA-EGCG nanoreactor in vitro and in vivo. Results: DOX@MTP/HA-EGCG nanoreactors were able to disassemble, resulting in escape of their components from lysosomes and precise release of DOX, Fe3+, and EGCG in the tumor cells. HA-EGCG depleted glutathione to amplify oxidative stress and enhance chemodynamic therapy. The results of in vivo experiments suggested that DOX@MTP/HA-EGCG specifically accumulates at the CD44-overexpressing GL261 tumor sites and that sustained release of DOX and Fe3+ induced a distinct therapeutic outcome. Conclusions: The findings suggested the developed nanoreactor has promising potential as a future GL261 glioblastoma therapy.

Hyaluronic Acid-Conjugated Nanoparticles for the Targeted Delivery of Cabazitaxel to CD44-Overexpressing Glioblastoma Cells.

In decades, the efficiency of glioma therapy is far from satisfaction due to the inability of most therapeutics to accumulate at the glioblastoma (GBM) site. Therefore, it is urgent to develop novel tumor-targeted delivery systems for more optimized and effective glioma treatment. In this study, hyaluronic acid modified MPEG-PDLLA polymer (HAML) nanoparticles were used to encapsulate the cabazitaxel (Cab), creating Cab loaded HAML nanoparticles (Cab/HAML NPs) for glioma therapy both in vitro and in vivo. MTT assay and apoptotic study indicated Cab/HAML NPs induced a significant cell growth inhibition and more apoptosis of C6 cells than free Cab in vitro. In vivo study showed that Cab/HAML NPs could significantly improve chemotherapeutic effect to C6 tumor-bearing rats compared with free Cab. The median survival rate of Cab/HAML NPs-treated groups (30 days) was remarkably longer than the other groups treated with control (20 days), free Cab (19 days) and Cab/ML NPs (26 days). Immunohistochemical analysis revealed that Cab/HAML NPs improved Cab's anti-tumor effect via improvement of tumor cell apoptosis, inhibition of tumor cell proliferation and a significant decrease in tumor angiogenesis. Together, our study suggested that Cab/HAML NPs might show promise for application to glioma therapy.