Immunogenic hydrogel toolkit disturbing residual tumor “seeds” and pre-metastatic “soil” for inhibition of postoperative tumor recurrence and metastasis

Zhou, Minglu; Zuo, Qingting; Huang, Yuan; Li, Lian

doi:10.1016/j.apsb.2022.02.017

Cited by 27 publications

(22 citation statements)

References 38 publications

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Section: Resultssupporting

confidence: 89%

“…As compared with the hydrogel precursor of PVA solution whose adhesiveness was too low to be determined, ACCO@Gel had apparent adhesive capacity to porcine skin, with tensile and shear adhesion strengths of ∼5.8 and ∼56 kPa, respectively. Similar with other studies 32,33 that utilized a PVA-based hydrogel for local drug delivery and biomedical purposes, we have also observed that the hydrogel scaffold could be peritumorally formed after in situ injection and adhere to the surrounding tissues of residual tumor after 4 days post tumor resection (Figure S2E). Uniform and ordered dispersion of the cell nucleus, cytoplasm, and oncolysis-induced CRT exposure in ACCO@ Gel was observed by three-dimensional scanning using confocal laser scanning microscopy, suggesting that the hydrogel matrix could effectively maintain abundant antigen sources and adjuvantic DAMPs (Figure 2C).…”

Section: Resultssupporting

confidence: 88%

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Trauma-Responsive Scaffold Synchronizing Oncolysis Immunization and Inflammation Alleviation for Post-Operative Suppression of Cancer Metastasis

Zhang

Zhou

et al. 2022

ACS Nano

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Tumor surgery can create an inflammatory trauma to aggravate residual tumor “seed” to colonize pre-metastatic niches (PMNs) “soil” at secondary sites, thereby promoting post-operative metastasis. However, two-pronged strategies for post-surgical elimination of asynchronous “seeds” and “soil” at different regions are currently lacking. Here, we have designed a hydrogel that can be injected into a resection cavity, where it immediately forms a scaffold and gradually degrades responding to enriched reactive oxygen species at adjacent trauma for local delivery and on-demand release of autologous cancer cells succumbing to oncolysis (ACCO) and anti-inflammatory agent. The autologous cell source self-provides a whole array of tumor-associated antigens, and the oncolysis orchestration of a subcellular cascade confers a self-adjuvanting property, together guaranteeing high immunogenicity of the ACCO vaccine that enables specific antitumor immunization. In parallel, inflammation alleviation exerted bidirectional functions to reshape the local immune landscape and resuscitate ACCO, leading to the eradication of residual tumor “seeds” while simultaneously intercepting the “seed–soil” crosstalk to normalize distant lung leading to regression of pre-existing PMN “soil”. As a result, regional and metastatic recurrence were completely thwarted. Together, this framework synchronizing oncolysis immunization and inflammation alleviation provides an effective option for post-operative suppression of metastasis.

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Section: Resultssupporting

confidence: 89%

Section: Resultssupporting

confidence: 88%

Trauma-Responsive Scaffold Synchronizing Oncolysis Immunization and Inflammation Alleviation for Post-Operative Suppression of Cancer Metastasis

Zhang

Zhou

et al. 2022

ACS Nano

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“…Transforming growth factor-β1 (TGF-β1) is a multifunctional cytokine involved in angiogenesis, epithelial to mesenchymal transition (EMT) and immune escape of tumor cells [ 83 , 175 , 179 ]. Canonical therapeutics for TGF-β1 blocking are antisense oligonucleotides and antibodies.…”

Section: The “Blue Ocean”: Unexploited and Less-developed Targets For...mentioning

confidence: 99%

Small-Molecule PROTACs for Cancer Immunotherapy

Liu¹,

Zhang²,

Xiang³

et al. 2022

Molecules

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Unsatisfactory physicochemical properties of macromolecular drugs seriously hinder their application in tumor immunotherapy. However, these problems can be effectively solved by small-molecule compounds. In the promising field of small-molecule drug development, proteolysis targeting chimera (PROTAC) offers a Cancer Patients. Bosn. J. Basic novel mode of action in the interactions between small molecules and therapeutic targets (mainly proteins). This revolutionary technology has shown considerable impact on several proteins related to tumor survival but is rarely exploited in proteins associated with immuno-oncology up until now. This review attempts to comprehensively summarize the well-studied and less-developed immunological targets available for PROTAC technology, as well as some targets to be explored, aiming to provide more options and opportunities for the development of small-molecule-based tumor immunotherapy. In addition, some novel directions that can magnify and broaden the protein degradation efficiency are mentioned to improve PROTAC design in the future.

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“…Rather than systemic delivery, local application of antibodies within tumoral and peritumoral regions is an excellent approach to obviate the overactivation of the immune system ( 66 ). Melief et al.…”

Section: Nanotechnology Facilitates Immune Checkpoint Blockade Therapymentioning

confidence: 99%

Advancing immune checkpoint blockade in colorectal cancer therapy with nanotechnology

Liu

Xiang²,

Zheng³

et al. 2022

Front. Immunol.

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Immune checkpoint blockade (ICB) has gained unparalleled success in the treatment of colorectal cancer (CRC). However, undesired side effects, unsatisfactory response rates, tumor metastasis, and drug resistance still hinder the further application of ICB therapy against CRC. Advancing ICB with nanotechnology can be game-changing. With the development of immuno-oncology and nanomaterials, various nanoplatforms have been fabricated to enhance the efficacy of ICB in CRC treatment. Herein, this review systematically summarizes these recent nano-strategies according to their mechanisms. Despite their diverse and complex designs, these nanoplatforms have four main mechanisms in enhancing ICB: 1) targeting immune checkpoint inhibitors (ICIs) to tumor foci, 2) increasing tumor immunogenicity, 3) remodeling tumor microenvironment, and 4) pre-sensitizing immune systems. Importantly, advantages of nanotechnology in CRC, such as innovating the mode-of-actions of ICB, modulating intestinal microbiome, and integrating the whole process of antigen presentation, are highlighted in this review. In general, this review describes the latest applications of nanotechnology for CRC immunotherapy, and may shed light on the future design of ICB platforms.

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Immunogenic hydrogel toolkit disturbing residual tumor “seeds” and pre-metastatic “soil” for inhibition of postoperative tumor recurrence and metastasis

Cited by 27 publications

References 38 publications

Trauma-Responsive Scaffold Synchronizing Oncolysis Immunization and Inflammation Alleviation for Post-Operative Suppression of Cancer Metastasis

Trauma-Responsive Scaffold Synchronizing Oncolysis Immunization and Inflammation Alleviation for Post-Operative Suppression of Cancer Metastasis

Small-Molecule PROTACs for Cancer Immunotherapy

Advancing immune checkpoint blockade in colorectal cancer therapy with nanotechnology

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