Improved Efficacy and Reduced Toxicity Using a Custom-Designed Irinotecan-Delivering Silicasome for Orthotopic Colon Cancer

Liu, Xiangsheng; Jiang, Jinhong; Chan, Ryan; Ji, Ying; Lu, Jianqin; Liao, Yu‐Pei; Okene, Michael; Lin, Joshua; Lin, Paulina; Chang, Chong Hyun; Wang, Xiang; Tang, Ivanna; Zheng, Emily; Qiu, Waveley; Wainberg, Zev A.; Nel, André E.; Meng, Huan

doi:10.1021/acsnano.8b06164

Cited by 89 publications

(86 citation statements)

References 102 publications

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“…Nonetheless, from day 10, tumor persisted and progressed to lethal CRC in only 25-35% of mice, whereas the remaining 65-75% of animals spontaneously rejected CRC tumors. Other research groups have previously performed similar orthotopic-implantation of parental MC38 cells or MC38-fLuc in the colon of B6 mice [37][38][39]. These studies have reported a rather low tumor incidence (25% to 40%) between 4 to 6 weeks post-implantation, which was explained by a poor tumor intake.…”

Section: Discussionmentioning

confidence: 98%

“…In addition, we initially optimized CRC development by injecting 1x10 6 MC38 cells, which represents a lower tumor-cell dose than used in the above cited studies (i.e. 2x10 6 MC38 cells) [37][38][39]. Injecting three times more cells (3x10 6 ), to optimize the chances of tumor implantation, did not dramatically increase the percentage of mice developing a progressive CRC profile, thus implying that the number of injected cancer cells has a negligible impact on the two CRC developmental profiles.…”

Section: Discussionmentioning

confidence: 99%

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Colon-specific immune microenvironment regulates cancer progression versus rejection

Trimaglio

Tilkin–Mariamé

Féliu

et al. 2020

Preprint

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Background:Immunotherapies have achieved clinical benefit in many types of cancer but remain limited to a subset of patients in colorectal cancer (CRC). Resistance to immunotherapy can be attributed in part to tissue-specific factors constraining antitumor immunity. Thus, a better understanding of how the colon microenvironment shapes the immune response to CRC is needed to identify mechanisms of resistance to immunotherapies and guide the development of novel therapeutics. Methods:In an orthotopic mouse model of MC38-CRC, tumor progression was monitored by bioluminescence imaging and the immune signatures were assessed at a transcriptional level using NanoString and at a cellular level by flow cytometry.Results: Despite initial tumor growth in all mice, only 25 to 35% of mice developed a progressive lethal CRC while the remaining animals spontaneously rejected their solid tumor.No tumor rejection was observed in the absence of adaptive immunity, nor when MC38 cells were injected in non-orthotopic locations, subcutaneously or into the liver. We observed that progressive CRC tumors exhibited a protumor immune response, characterized by a regulatory T-lymphocyte pattern, discernible shortly post-tumor implantation, as well as suppressive myeloid cells. In contrast, tumor-rejecting mice presented an early inflammatory response and an antitumor microenvironment enriched in CD8 + T cells. Conclusions:Taken together, our data demonstrate the role of the colon microenvironment in regulating the balance between anti or protumor immune responses. While emphasizing the relevance of the CRC orthotopic model, they set the basis for exploring the impact of the identified signatures in colon cancer response to immunotherapy.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Colon-specific immune microenvironment regulates cancer progression versus rejection

Trimaglio

Tilkin–Mariamé

Féliu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…After experimenting with ≈70 reaction conditions in an iterative optimization approach, it is possible to accomplish ≈120 g batch sizes of biocompatible MSNPs in ≈20 L volume ( Figure 6C). [157] Since the LB is supported, the improved stability of the silicasome was associated with less API leakage systemically, which was experimentally proven in the case of irinotecan delivery. [156] We have tested our irinotecan silicasome in an orthotopic Kras-derived PDAC model as well as a colorectal cancer (CRC) orthotopic model.…”

Section: Consideration Beyond Liposomes-new Challenges For the Next Smentioning

confidence: 95%

“…[156] We have tested our irinotecan silicasome in an orthotopic Kras-derived PDAC model as well as a colorectal cancer (CRC) orthotopic model. [157] The latter model was selected because irinotecan was approved as a monotherapy for CRC management. The data demonstrated that the silicasome delivered significantly increased drug concentrations at the orthotopic tumor sites compared to liposomes (in-house synthesized or commercial irinotecan liposome Onivyde), leading to superior anticancer effect (including treating metastases) in vivo ( Figure 6D).…”

Section: Consideration Beyond Liposomes-new Challenges For the Next Smentioning

confidence: 99%

Safety Considerations of Cancer Nanomedicine—A Key Step toward Translation

Liu

Tang

Wainberg

et al. 2020

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The rate of translational effort of nanomedicine requires strategic planning of nanosafety research in order to enable clinical trials and safe use of nanomedicine in patients. Herein, the experiences that have emerged based on the safety data of classic liposomal formulations in the space of oncology are discussed, along with a description of the new challenges that need to be addressed according to the rapid expansion of nanomedicine platform beyond liposomes. It is valuable to consider the combined use of predictive toxicological assessment supported by deliberate investigation on aspects such as absorption, distribution, metabolism, and excretion (ADME) and toxicokinetic profiles, the risk that may be introduced during nanomanufacture, unique nanomaterials properties, and nonobvious nanosafety endpoints, for example. These efforts will allow the generation of investigational new drug‐enabling safety data that can be incorporated into a rational infrastructure for regulatory decision‐making. Since the safety assessment relates to nanomaterials, the investigation should cover the important physicochemical properties of the material that may lead to hazards when the nanomedicine product is utilized in humans.

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“…Second, different kinds of nanoparticles with their own merits can be integrated into one hierarchically hybrid nanoplatform, resulting in synergistic action. In the case of hybridization of liposome and mesoporous silica nanoparticle (MSN), when the supported lipid bilayer (SLB) from liposome is deposited on the MSN cores, the hybrid SLB–MSN structure can be obtained . Through the synergistic action of SLB and MSN, stable and high drug loading, on‐demand release, and improved biocompatibility have been simultaneously achieved .…”

Section: Introductionmentioning

confidence: 99%

Hierarchically Nanostructured Hybrid Platform for Tumor Delineation and Image‐Guided Surgery via NIR‐II Fluorescence and PET Bimodal Imaging

Zhang

Zhou

Chen

et al. 2019

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Bimodal imaging with fluorescence in the second near infrared window (NIR‐II) and positron emission tomography (PET) has important significance for tumor diagnosis and management because of complementary advantages. It remains challenging to develop NIR‐II/PET bimodal probes with high fluorescent brightness. Herein, bioinspired nanomaterials (melanin dot, mesoporous silica nanoparticle, and supported lipid bilayer), NIR‐II dye CH‐4T, and PET radionuclide 64Cu are integrated into a hybrid NIR‐II/PET bimodal nanoprobe. The resultant nanoprobe exhibits attractive properties such as highly uniform tunable size, effective payload encapsulation, high stability, dispersibility, and biocompatibility. Interestingly, the incorporation of CH‐4T into the nanoparticle leads to 4.27‐fold fluorescence enhancement, resulting in brighter NIR‐II imaging for phantoms in vitro and in situ. Benefiting from the fluorescence enhancement, NIR‐II imaging with the nanoprobe is carried out to precisely delineate and resect tumors. Additionally, the nanoprobe is successfully applied in tumor PET imaging, showing the accumulation of the nanoprobe in a tumor with a clear contrast from 2 to 24 h postinjection. Overall, this hierarchically nanostructured platform is able to dramatically enhance fluorescent brightness of NIR‐II dye, detect tumors with NIR‐II/PET imaging, and guide intraoperative resection. The NIR‐II/PET bimodal nanoprobe has high potential for sensitive preoperative tumor diagnosis and precise intraoperative image‐guided surgery.

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Improved Efficacy and Reduced Toxicity Using a Custom-Designed Irinotecan-Delivering Silicasome for Orthotopic Colon Cancer

Cited by 89 publications

References 102 publications

Colon-specific immune microenvironment regulates cancer progression versus rejection

Colon-specific immune microenvironment regulates cancer progression versus rejection

Safety Considerations of Cancer Nanomedicine—A Key Step toward Translation

Hierarchically Nanostructured Hybrid Platform for Tumor Delineation and Image‐Guided Surgery via NIR‐II Fluorescence and PET Bimodal Imaging

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