Whole tumor cell lysates (TCL) have been implemented as tumor antigens for cancer vaccine development, although clinical outcomes of TCL-based antitumor immunotherapy remain unsatisfactory. In order to improve the efficacy of TCL-based vaccines, biomaterials have been employed to enhance antigen delivery and presentation. Here, we have developed chitosan nanoparticles (CTS NPs) with surface mannose (Man) moieties for specific dendritic cells (DCs) targeting (Man-CTS NPs). The Man-CTS NPs were then loaded with TCL generated from B16 melanoma cells (Man-CTS-TCL NPs) for in vitro and in vivo assessment. Potency of the Man-CTS-TCL NPs as cancer vaccine was also assessed in vivo by immunization of mice with Man-CTS-TCL NPs followed by re-challenge with B16 melanoma cell inoculation. We have shown here that Man-CTS-TCL NPs promote bone marrow-derived dendritic cells (BMDCs) maturation and antigen presentation in vitro. In vivo evaluation further demonstrated that the Man-CTS-TCL NPs were readily taken up by endogenous DCs within the draining lymph node (DLN) following subcutaneous administration accompanied by increasing in serum IFN-γ and IL-4 levels. Tumor growth was also significantly delayed in mice primed with Man-CTS-TCL NPs vaccine, attributable at least in part to cytotoxic T lymphocytes response. Moreover, Man-CTS-TCL NPs vaccine also exhibited therapeutic effects in mice with melanoma. Thus, we report here the Man-CTS-TCL NPs as effective anti-tumor vaccine for cancer immunotherapy.

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Nanoparticles have been extensively explored as effective means to deliver chemotherapeutic agents or photosensitizers for chemotherapy or photodynamic therapy (PDT) against cancer. In the present work, pheophorbide A (PheoA), a hydrophobic photosensitizer, was conjugated via a redox-sensitive disulfide linkage to alginate (PheoA-ALG). Anticancer agent, doxorubicin (DOX), was also loaded within the PheoA-ALG nanoparticles (DOX/PheoA-ALG NPs) and used as drug carriers for combinational antitumor treatment. The DOX/PheoA-ALG NPs were spherical in shape with a uniform diameter of approximately 210 nm. Redox-responsive drug releasing properties were shown by the DOX/PheoA-ALG NPs, with an accelerated amount of DOX and PheoA release observed in the presence of a high glutathione level (10 mM). Cellular uptake results showed that DOX/PheoA-ALG NPs were readily taken up by B16 tumor cells (murine melanoma) and enhanced DOX and PheoA uptake were detectable in the DOX/PheoA-ALG NPs-treated B16 cells in comparison to carrier free drugs. DOX/PheoA-ALG NPs also elicited intracellular ROS generation, which leads to enhanced toxicity in B16 cells. In vivo studies using B16 tumor-bearing mice further demonstrated that DOX/PheoA-ALG NPs were preferentially accumulated in tumor tissues, resulting in substantial inhibition of B16 tumor growth by chemotherapy and photodynamic therapy, which is also attributable to DOX/PheoA-ALG NP-elicited increase of serum INF-λ levels. Our results demonstrate a major potential of DOX/PheoA-ALG NPs for combinational cancer therapy.

Background/Aims: The endocannabinoid signalling (ECS) system has been known to regulate glucose homeostasis. Previous studies have suggested that the cannabinoid 2 (CB₂) receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance. Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB₂ receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD)/streptozotocin (STZ)-induced mice. Methods: Diabetes was induced in male ICR mice by HFD/STZ and exposed to a CB₂ receptor agonist, SER601, for 2- or 4-weeks via subcutaneous implantation of osmotic minipumps. Glucose and insulin tolerance tests were performed at the end of treatment. Islets were isolated for assessment of β-cell function. Pancreases and skeletal muscles were also obtained for histological analyses. Results: Despite a lack of impact on glucose tolerance, substantial improvement on insulin sensitivity was observed in SER601-treated mice, which could partly be attributed to improved islet β-cell function, shown as increased glucose-induced insulin secretion and insulin content. No changes on islet macrophage infiltration or skeletal muscle fat deposition were detectable from SER601-treated mice. However, a major decrease in body weight was recorded at the end of 4-week SER601 exposure, accompanied by a lack of epididymal adipose mass in SER601-treated mice. Conclusion: Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity. Thus, the CB₂ receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.