Optimizing Advances in Nanoparticle Delivery for Cancer Immunotherapy

Caster, Joseph M.; Callaghan, Cameron; Seyedin, Steven N.; Henderson, Kelly W.; Sun, Bo; Wang, Andrew Z.

doi:10.1016/j.addr.2019.07.009

Cited by 47 publications

(33 citation statements)

References 158 publications

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“…For example, a nanoparticle-based approach targeting collagenase in hypovascular pancreatic ductal adenocarcinoma had the goal of demonstrating increased drug penetration after nanoparticle treatment (Zinger et al, 2019). Similarly, novel nano-immunotherapies in development target phagocytic cells like macrophages or antigen presenting cells within the TME (Caster et al, 2019).…”

Section: Three-dimensional In Vitro and Ex Vivo Models Of The Cancer mentioning

confidence: 99%

Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis

Frieboes

Raghavan

Godin

2020

Front. Bioeng. Biotechnol.

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The tumor microenvironment (TME) presents a challenging barrier for effective nanotherapy-mediated drug delivery to solid tumors. In particular for tumors less vascularized than the surrounding normal tissue, as in liver metastases, the structure of the organ itself conjures with cancer-specific behavior to impair drug transport and uptake by cancer cells. Cells and elements in the TME of hypovascularized tumors play a key role in the process of delivery and retention of anti-cancer therapeutics by nanocarriers. This brief review describes the drug transport challenges and how they are being addressed with advanced in vitro 3D tissue models as well as with in silico mathematical modeling. This modeling complements network-oriented techniques, which seek to interpret intra-cellular relevant pathways and signal transduction within cells and with their surrounding microenvironment. With a concerted effort integrating experimental observations with computational analyses spanning from the molecular-to the tissue-scale, the goal of effective nanotherapy customized to patient tumor-specific conditions may be finally realized.

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Section: Three-dimensional In Vitro and Ex Vivo Models Of The Cancer mentioning

confidence: 99%

Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis

Frieboes

Raghavan

Godin

2020

Front. Bioeng. Biotechnol.

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“…[ 2,3 ] During the past decade, immunotherapies, such as vaccination, checkpoint blockade, and chimeric antigen receptor T cell therapy, were recognized as the most promising approaches to treat cancers. [ 4,5 ] However, although these immunotherapy approaches have proven great potential in the treatment of melanoma, prostate cancer, and a growing list of other malignancies, their efficacy in glioblastoma treatment is insufficient to date. [ 6,7 ] For example, a phase III study showed that a peptide vaccine Rindopepimut in combination with temozolomide failed to improve the median overall survival (OS) of GBM patients.…”

Section: Methodsmentioning

confidence: 99%

A Virus‐Mimicking Nucleic Acid Nanogel Reprograms Microglia and Macrophages for Glioblastoma Therapy

et al. 2021

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Immunotherapy is recognized as one of the most promising approaches to treat cancers. However, its effect in glioblastoma (GBM) treatment is insufficient, which can in part be attributed to the immunosuppressive tumor microenvironment (TME). Microglia and macrophages are the main immune infiltrating cells in the TME of GBM. Unfortunately, instead of initiating the anti‐tumor response, GBM‐infiltrating microglia and macrophages switch to a tumor‐promoting phenotype (M2), and support tumor growth, angiogenesis, and immunosuppression by the release of cytokines. In this work, a virus‐mimicking membrane‐coated nucleic acid nanogel Vir‐Gel embedded with therapeutic miRNA is developed, which can reprogram microglia and macrophages from a pro‐invasive M2 phenotype to an anti‐tumor M1 phenotype. By mimicking the virus infection process, Vir‐Gel significantly enhances the targetability and cell uptake efficiency of the miR155‐bearing nucleic acid nanogel. In vivo evaluations demonstrate that Vir‐Gel apparently prolongs the circulation lifetime of miR155 and endows it with an active tumor‐targeting capability and excellent tumor inhibition efficacy. Owing to its noninvasive feature and effective delivery capability, the virus‐mimicking nucleic acid nanogel provides a general and convenient platform that can successfully treat a wide range of diseases.

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“…[172] However, there are several shortcomings of current cancer immunotherapy, including low immune responses, poor tumor targeting, and severe side effects of the immunotherapeutics. [173] Prodrug nanomedicines integrate the advantages of prodrugs and nanotechnology to enhance the efficiency and safety of tumor immunotherapy relative to the conventional nanomedicine. [174] Prodrug nanomedicines possess a broad toolkit to improve prodrug stability during circulation and to enhance the bioavailability of codelivered drugs with different pharmacokinetics profiles.…”

Section: Summary and Perspectivementioning

confidence: 99%

Engineering Prodrug Nanomedicine for Cancer Immunotherapy

et al. 2020

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Immunotherapy has shifted the clinical paradigm of cancer management. However, despite promising initial progress, immunotherapeutic approaches to cancer still suffer from relatively low response rates and the possibility of severe side effects, likely due to the low inherent immunogenicity of tumor cells, the immunosuppressive tumor microenvironment, and significant interand intratumoral heterogeneity. Recently, nanoformulations of prodrugs have been explored as a means to enhance cancer immunotherapy by simultaneously eliciting antitumor immune responses and reversing local immunosuppression. Prodrug nanomedicines, which integrate engineering advances in chemistry, oncoimmunology, and material science, are rationally designed through chemically modifying small molecule drugs, peptides, or antibodies to yield increased bioavailability and spatiotemporal control of drug release and activation at the target sites. Such strategies can help reduce adverse effects and enable codelivery of multiple immune modulators to yield synergistic cancer immunotherapy. In this review article, recent advances and translational challenges facing prodrug nanomedicines for cancer immunotherapy are overviewed. Last, key considerations are outlined for future efforts to advance prodrug nanomedicines aimed to improve antitumor immune responses and combat immune tolerogenic microenvironments.

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Optimizing Advances in Nanoparticle Delivery for Cancer Immunotherapy

Cited by 47 publications

References 158 publications

Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis

Modeling of Nanotherapy Response as a Function of the Tumor Microenvironment: Focus on Liver Metastasis

A Virus‐Mimicking Nucleic Acid Nanogel Reprograms Microglia and Macrophages for Glioblastoma Therapy

Engineering Prodrug Nanomedicine for Cancer Immunotherapy

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