The Experts below are selected from a list of 717 Experts worldwide ranked by ideXlab platform
Goran Angelovski - One of the best experts on this subject based on the ideXlab platform.
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Investigations into the Effects of Linker Length Elongation on the Behaviour of Calcium-responsive MRI Probes
2019Co-Authors: Liam Connah, Vincent Truffault, Goran AngelovskiAbstract:Understanding the relationship between chemical structure and the effectiveness of Bioresponsive magnetic resonance imaging contrast agents can offer help to identify key components required for the future development of such probes. Here, we report the development and characteristion of two novel monomeric bifunctional chelators, whose paramagnetic metal complexes can serve as calcium-responsive smart contrast agent (SCA). Specifically, relaxometric titrations, luminescence lifetime measurements, NMR studies and NMR diffusion experiments were carried out to assess the behaviour of each system. Overall, our findings demonstrate the impact of subtle changes to the structure of such probes, affecting a range of properties and their coordination behaviour. Through the understanding of such changes, fine tuning of future SCA designs which show optimal changes in relaxivity can be achieved
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synergy of key properties promotes dendrimer conjugates as prospective ratiometric Bioresponsive magnetic resonance imaging probes
Biomacromolecules, 2018Co-Authors: Liam Connah, Goran AngelovskiAbstract:Bioresponsive or smart contrast agents (SCAs) sensitive to Ca2+ are of extreme interest in the development of functional magnetic resonance imaging (MRI) techniques as they can aid in tracking neural activity in vivo. To this end, the design of macromolecular systems based on nanoscaffolds such as dendrimers functionalized with multiple MRI contrast agents has been used to conveniently increase the local concentration of paramagnetic MR reporters and slow the diffusion time of the probe, which are favorable in vivo characteristics. Moreover, previous studies with Ca-sensitive dendrimeric MRI probes revealed favorable properties crucial in the development of a ratiometric T2/T1-imaging method that provided a higher contrast-to-noise ratio compared to conventional T1- or T2-weighted imaging protocols. We therefore developed a series of novel dendrimeric MRI probes (DCAs) with differing structural properties and charge distributions. We thoroughly studied their features such as the relaxometric behavior and ...
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heading toward macromolecular and nanosized Bioresponsive mri probes for successful functional imaging
Accounts of Chemical Research, 2017Co-Authors: Goran AngelovskiAbstract:ConspectusThe quest for Bioresponsive or smart contrast agents (SCAs) in molecular imaging, in particular magnetic resonance imaging (MRI), is progressively increasing since they allow for the monitoring of essential biological processes on molecular and cellular levels in a dynamic fashion. These are offshoot molecules of common contrast agents that are sensitive to biochemical changes in their environment, capable of reporting on such changes by inducing MRI signal alteration. Various mechanistic approaches and different types of SCAs have been developed in order to visualize desired processes, using diverse imaging protocols and methods. To date, the most frequently exploited probes are paramagnetic molecules that change longitudinal or transverse relaxation at proton frequency, or so-called T1- and T2-weighted probes, respectively. Moreover, SCAs operating by the chemical exchange saturation transfer mechanism, suitable for 19F MRI or possessing hyperpolarized nuclei have also appeared in the past dec...
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what we can really do with Bioresponsive mri contrast agents
Angewandte Chemie, 2016Co-Authors: Goran AngelovskiAbstract:Bioresponsive MRI contrast agents hold great promise for monitoring major physiological and pathological processes in a non-invasive manner. They are capable of altering the acquired MRI signal as a consequence of changes in their microenvironment, thus allowing real-time functional reporting in living organisms. Importantly, chemistry offers diverse solutions for the design of agents which respond to a great number of specific targets. However, the path to the successful utilization of these biomarkers in the desired functional MRI studies involves careful consideration of multiple scientific, technical, and practical issues across various research disciplines. This Minireview highlights the critical steps for planning and executing such multidisciplinary projects with an aim to substantially improve our knowledge of essential biological processes.
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innovative design of ca sensitive paramagnetic liposomes results in an unprecedented increase in longitudinal relaxivity
Biomacromolecules, 2016Co-Authors: Francesca Garello, Sandip Vibhute, Serhat Gunduz, N K Logothetis, Enzo Terreno, Goran AngelovskiAbstract:Bioresponsive MRI contrast agents sensitive to Ca(II) fluctuations may play a critical role in the development of functional molecular imaging methods to study brain physiology or abnormalities in muscle contraction. A great challenge in their chemistry is the preparation of probes capable of inducing a strong signal variation that could be detected in a robust way. To this end, the incorporation of small molecular weight Bioresponsive agents into nanocarriers can improve the overall properties in a few ways: (i) the agent can be delivered into the tissue of interest, increasing the local concentration; (ii) its biokinetic properties and retention time will improve; (iii) the high molecular weight and size of the nanocarrier may cause additional changes in the MRI signal and raise the chances for their detection in functional experiments. In this work, we report the preparation of the new class of liposome-based, Ca-sensitive MRI agents. We synthesized a novel amphiphilic ligand which was incorporated int...
Zhiyuan Zhong - One of the best experts on this subject based on the ideXlab platform.
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small traceable endosome disrupting and Bioresponsive click nanogels fabricated via microfluidics for cd44 targeted cytoplasmic delivery of therapeutic proteins
ACS Applied Materials & Interfaces, 2019Co-Authors: Ke Huang, Chao Deng, Zhehong Zhu, Jiakun Guo, Guanglin Wang, Zhiyuan ZhongAbstract:Nanogels (NG) are among the most ideal cytoplasmic protein delivery vehicles; however, their performance is suboptimal, partly owing to relatively big size, poor cell uptake, and endosomal entrapment. Here, we developed small, traceable, endosome-disrupting, and Bioresponsive hyaluronic acid NG (HA-NG) for CD44-targeted intracellular delivery of therapeutic proteins. With microfluidics and catalyst-free photo-click cross-linking, HA-NG with hydrodynamic diameters of ca. 80 and 150 nm, strong green fluorescence and efficient loading of various proteins including saporin (Sap), cytochrome C, herceptin, immunoglobulin G (IgG), and bovine serum albumin could be fabricated. Interestingly, 80 nm-sized HA-NG revealed clearly better cellular uptake than its 150 nm counterparts in both CD44-negative U87 cancer cells and CD44-positive 4T1 and MDA-MB-231 cells. Moreover, small NG exhibited accelerated endosomal escape, which was further boosted by introducing GALA, a pH-sensitive fusogenic peptide. Accordingly, Sap-loaded small and GALA-functionalized HA-NG showed the highest cytotoxicity in CD44-positive MDA-MB-231, 4T1, A549, and SMMC-7721 cancer cells. The biodistribution studies demonstrated that 80 nm-sized HA-NG displayed significantly greater tumor uptake as well as penetration in MDA-MB-231 human breast tumor xenografts than its 150 nm counterparts, whereas the introduction of GALA had no detrimental effect on tumor accumulation. Small, endosome-disrupting, and Bioresponsive HA-NG with easy and controlled fabrication hold a great potential for targeted protein therapy.
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Bioresponsive functional nanogels as an emerging platform for cancer therapy
Expert Opinion on Drug Delivery, 2018Co-Authors: Dechun Huang, Hongliang Qian, Haishi Qiao, Wei Chen, Jan Feijen, Zhiyuan ZhongAbstract:Introduction Bioresponsive nanogels with a crosslinked three-dimensional structure and an aqueous environment that undergo physical or chemical changes including swelling and dissociation in response to biological signals such as mild acidity, hyperthermia, enzymes, reducing agents, reactive oxygen species (ROS), and adenosine-5'-triphosphate (ATP) present in tumor microenvironments or inside cancer cells have emerged as an appealing platform for targeted drug delivery and cancer therapy. Areas covered This review highlights recent designs and development of Bioresponsive nanogels for facile loading and triggered release of chemotherapeutics and biotherapeutics. The in vitro and in vivo antitumor performances of drug-loaded nanogels are discussed. Expert opinion Bioresponsive nanogels with an excellent stability and safety profile as well as fast response to biological signals are unique systems that mediate efficient and site-specific delivery of anticancer drugs, in particular macromolecular drugs like proteins, siRNA and DNA, leading to significantly enhanced tumor therapy compared with the non-responsive counterparts. Future research has to be directed to the development of simple, tumor-targeted and Bioresponsive multifunctional nanogels, which can be either constructed from natural polymers with intrinsic targeting ability or functionalized with targeting ligands. We anticipate that rationally designed nanotherapeutics based on Bioresponsive nanogels will become available for future clinical cancer treatment. Abbreviations AIE, aggregation-induced emission; ATP, adenosine-5'-triphosphate; ATRP, atom transfer radical polymerization; BSA, bovine serum albumin; CBA, cystamine bisacrylamide; CC, Cytochrome C; CDDP, cisplatin; CT, computed tomography; DC, dendritic cell; DiI, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate; DOX, doxorubicin; dPG, dendritic polyglycerol; DTT, dithiothreitol; EAMA, 2-(N,N-diethylamino)ethyl methacrylate; EPR, enhanced permeability and retention; GrB, granzyme B; GSH, glutathione tripeptide; HA, hyaluronic acid; HAase, hyaluronidases; HCPT, 10-Hydroxycamptothecin; HEP, heparin; HPMC, hydroxypropylmethylcellulose; LBL, layer-by-layer; MTX, methotrexate; NCA, N-carboxyanhydride; OVA, ovalbumin; PAH, poly(allyl amine hydrochloride); PBA, phenylboronic acid; PCL, polycaprolactone; PDEAEMA, poly(2-diethylaminoethyl methacrylate); PDGF, platelet derived growth factor; PDPA, poly(2-(diisopropylamino)ethyl methacrylate); PDS, pyridyldisulfide; PEG, poly(ethylene glycol); PEGMA, polyethyleneglycol methacrylate; PEI, polyethyleneimine; PHEA, poly(hydroxyethyl acrylate); PHEMA, poly(2-(hydroxyethyl) methacrylate; PNIPAM, poly(N-isopropylacrylamide); PMAA, poly(methacrylic acid); PPDSMA, poly(2-(pyridyldisulfide)ethyl methacrylate); PTX, paclitaxel; PVA, poly(vinyl alcohol); QD, quantum dot; RAFT, reversible addition-fragmentation chain transfer; RGD, Arg-Gly-Asp peptide; ROP, ring-opening polymerization; ROS, reactive oxygen species; TMZ, temozolomide; TRAIL, tumor necrosis factor-related apoptosis inducing ligand; VEGF, vascular endothelial growth factor.
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Lipoyl Ester Terminated Star PLGA as a Simple and Smart Material for Controlled Drug Delivery Application
Biomacromolecules, 2018Co-Authors: Xiuxiu Wang, Ru Cheng, Zhiyuan ZhongAbstract:PLGA, a copolymer of lactide and glycolide, is one of the most used biodegradable polymers that find a wide range of biomedical applications including drug delivery and tissue engineering. However, in spite of remarkable advancement, nanotherapeutics based on PLGA might have drawbacks of inadequate stability, drug leakage, and slow drug release at the tumor site, which reduces its targeting ability and therapeutic efficacy. Here, we report that direct modification of star PLGA ends with lipoic acid, a natural antioxidant present in our human body, affords a smart material (sPLGA-LA) that forms reversibly crosslinked and Bioresponsive multifunctional nanoparticles (sPLGA XNPs). Interestingly, sPLGA XNPs obtained in the presence of 23.0 wt % PEG–PDLLA displayed a small hydrodynamic size of 73 ± 1.2 nm, high stability against dilution and 10% serum, while fast destabilization under a reductive environment. Moreover, sPLGA XNPs achieved efficient loading of lipophilic anticancer drug model, doxorubicin (DOX),...
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Bioresponsive Chimaeric Nanopolymersomes Enable Targeted and Efficacious Protein Therapy for Human Lung Cancers in Vivo
2017Co-Authors: Weijing Yang, Fenghua Meng, Yifeng Xia, Yan Zou, Jian Zhang, Zhiyuan ZhongAbstract:Rapidly evolving protein technology has generated hundreds of therapeutic proteins that are promising for treating various human diseases. The clinical use of protein drugs remains, however, limited due to the absence of viable vehicles. Here, we report that anisamide-functionalized Bioresponsive chimaeric nanopolymersomes (Anis-BCPs) can efficiently load granzyme B (GrB), a potent apoptotic protein, and enable targeted and efficacious protein therapy for H460 human lung cancer in vivo. Anis-BCPs are readily obtained from poly(ethylene glycol)-b-poly(N-2-hydroxypropyl methacrylamide-g-lipoic acid)-b-poly(acrylic acid) triblock copolymer. Notably, GrB-loaded Anis-BCPs a display superior antitumor effect toward sigma receptor-overexpressing H460 lung cancer cells (IC50 = 7.8 nM). The in vivo studies reveal that Anis-BCPs have a long circulation time and remarkable tumor accumulation. Interestingly, GrB-loaded Anis-BCPs at 6.24 nmol GrB equiv/kg dose, given either in four injections or one single injection, effectively inhibit H460 tumor growth and significantly improve the survival rate for mice. These robust, Bioresponsive, and nontoxic chimaeric nanopolymersomes provide a potential platform for cancer protein therapy as well as basic research on intracellular functional proteins
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Bioresponsive polymeric nanotherapeutics for targeted cancer chemotherapy
Nano Today, 2015Co-Authors: Ru Cheng, Fenghua Meng, Chao Deng, Zhiyuan ZhongAbstract:Summary In recent years, Bioresponsive polymeric nanotherapeutics that facilitate tumor cell uptake and trigger drug release at the target site have emerged as a fascinating platform for safe and efficient cancer therapy. The naturally occurring environments such as tumor acidity, tumor extracellular enzymes like matrix metalloproteases (MMP), endo/lysosomal pH, elevated glutathione levels in the cytoplasm and cell nucleus, lysosomal enzymes, as well as reactive oxygen species (ROS) in the mitochondria have been exploited as potential internal stimuli to achieve active drug and protein release in the tumor tissue or cancer cells. These Bioresponsive nanosystems present several unique features such as no need of an external device, precision control over site of response (from tumor tissue down to cellular organelle level) following accumulation in the tumor via either passive or active targeting, and spontaneous activation in the tumor site or inside the tumor cells. In this review, we highlight the design rationale and recent exciting development of Bioresponsive polymeric nanotherapeutics for enhanced cancer treatments with low side effects.
Qian Chen - One of the best experts on this subject based on the ideXlab platform.
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Bioresponsive protein complex of apd1 and acd47 antibodies for enhanced immunotherapy
Nano Letters, 2019Co-Authors: Jinqiang Wang, Xudong Zhang, Qian Chen, Guojun Chen, Jiawen Chen, Jingjing Shen, Amanda ChanAbstract:Despite the promising efficacy of immune checkpoint blockade (ICB) in treating many types of cancers, the clinical benefits have often been restricted by the low objective response rates and systemic immune-related adverse events. Here, a Bioresponsive ICB treatment is developed based on the reactive oxygen species (ROS)-sensitive protein complex for controlled sequential release of anti- "don't eat me" signal antibody (aCD47) and antiprogrammed cell death protein 1 (aPD1), by leveraging the abundant ROS in the tumor microenvironment (TME). These protein complexes can also act as scavengers of ROS in the TME to reverse the immunosuppressive responses, thereby enhancing antitumor efficacy in vivo. In a melanoma cancer model, the synergistic antitumor efficacy was achieved, which was accompanied by enhanced T cell immune responses together with reduced immunosuppressive responses.
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a dual Bioresponsive drug delivery depot for combination of epigenetic modulation and immune checkpoint blockade
Advanced Materials, 2019Co-Authors: Huitong Ruan, Jinqiang Wang, Qian Chen, Guojun Chen, Di Wen, Hao ChengAbstract:Patients with advanced melanoma that is of low tumor-associated antigen (TAA) expression often respond poorly to PD-1/PD-L1 blockade therapy. Epigenetic modulators, such as hypomethylation agents (HMAs), can enhance the antitumor immune response by inducing TAA expression. Here, a dual Bioresponsive gel depot that can respond to the acidic pH and reactive oxygen species (ROS) within the tumor microenvironment (TME) for codelivery of anti-PD1 antibody (aPD1) and Zebularine (Zeb), an HMA, is engineered. aPD1 is first loaded into pH-sensitive calcium carbonate nanoparticles (CaCO3 NPs), which are then encapsulated in the ROS-responsive hydrogel together with Zeb (Zeb-aPD1-NPs-Gel). It is demonstrated that this combination therapy increases the immunogenicity of cancer cells, and also plays roles in reversing immunosuppressive TME, which contributes to inhibiting the tumor growth and prolonging the survival time of B16F10-melanoma-bearing mice.
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in situ sprayed Bioresponsive immunotherapeutic gel for post surgical cancer treatment
Nature Nanotechnology, 2019Co-Authors: Yuqi Zhang, Chao Wang, Jinqiang Wang, Xudong Zhang, Qian Chen, Guojun Chen, Di Wen, Guang Yang, Chen JiangAbstract:Cancer recurrence after surgical resection remains a significant cause of treatment failure. Here, we have developed an in situ formed immunotherapeutic Bioresponsive gel that controls both local tumour recurrence after surgery and development of distant tumours. Briefly, calcium carbonate nanoparticles pre-loaded with the anti-CD47 antibody are encapsulated in the fibrin gel and scavenge H+ in the surgical wound, allowing polarization of tumour-associated macrophages to the M1-like phenotype. The released anti-CD47 antibody blocks the 'don't eat me' signal in cancer cells, thereby increasing phagocytosis of cancer cells by macrophages. Macrophages can promote effective antigen presentation and initiate T cell mediated immune responses that control tumour growth. Our findings indicate that the immunotherapeutic fibrin gel 'awakens' the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread.
Jinqiang Wang - One of the best experts on this subject based on the ideXlab platform.
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Bioresponsive protein complex of apd1 and acd47 antibodies for enhanced immunotherapy
Nano Letters, 2019Co-Authors: Jinqiang Wang, Xudong Zhang, Qian Chen, Guojun Chen, Jiawen Chen, Jingjing Shen, Amanda ChanAbstract:Despite the promising efficacy of immune checkpoint blockade (ICB) in treating many types of cancers, the clinical benefits have often been restricted by the low objective response rates and systemic immune-related adverse events. Here, a Bioresponsive ICB treatment is developed based on the reactive oxygen species (ROS)-sensitive protein complex for controlled sequential release of anti- "don't eat me" signal antibody (aCD47) and antiprogrammed cell death protein 1 (aPD1), by leveraging the abundant ROS in the tumor microenvironment (TME). These protein complexes can also act as scavengers of ROS in the TME to reverse the immunosuppressive responses, thereby enhancing antitumor efficacy in vivo. In a melanoma cancer model, the synergistic antitumor efficacy was achieved, which was accompanied by enhanced T cell immune responses together with reduced immunosuppressive responses.
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a dual Bioresponsive drug delivery depot for combination of epigenetic modulation and immune checkpoint blockade
Advanced Materials, 2019Co-Authors: Huitong Ruan, Jinqiang Wang, Qian Chen, Guojun Chen, Di Wen, Hao ChengAbstract:Patients with advanced melanoma that is of low tumor-associated antigen (TAA) expression often respond poorly to PD-1/PD-L1 blockade therapy. Epigenetic modulators, such as hypomethylation agents (HMAs), can enhance the antitumor immune response by inducing TAA expression. Here, a dual Bioresponsive gel depot that can respond to the acidic pH and reactive oxygen species (ROS) within the tumor microenvironment (TME) for codelivery of anti-PD1 antibody (aPD1) and Zebularine (Zeb), an HMA, is engineered. aPD1 is first loaded into pH-sensitive calcium carbonate nanoparticles (CaCO3 NPs), which are then encapsulated in the ROS-responsive hydrogel together with Zeb (Zeb-aPD1-NPs-Gel). It is demonstrated that this combination therapy increases the immunogenicity of cancer cells, and also plays roles in reversing immunosuppressive TME, which contributes to inhibiting the tumor growth and prolonging the survival time of B16F10-melanoma-bearing mice.
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in situ sprayed Bioresponsive immunotherapeutic gel for post surgical cancer treatment
Nature Nanotechnology, 2019Co-Authors: Yuqi Zhang, Chao Wang, Jinqiang Wang, Xudong Zhang, Qian Chen, Guojun Chen, Di Wen, Guang Yang, Chen JiangAbstract:Cancer recurrence after surgical resection remains a significant cause of treatment failure. Here, we have developed an in situ formed immunotherapeutic Bioresponsive gel that controls both local tumour recurrence after surgery and development of distant tumours. Briefly, calcium carbonate nanoparticles pre-loaded with the anti-CD47 antibody are encapsulated in the fibrin gel and scavenge H+ in the surgical wound, allowing polarization of tumour-associated macrophages to the M1-like phenotype. The released anti-CD47 antibody blocks the 'don't eat me' signal in cancer cells, thereby increasing phagocytosis of cancer cells by macrophages. Macrophages can promote effective antigen presentation and initiate T cell mediated immune responses that control tumour growth. Our findings indicate that the immunotherapeutic fibrin gel 'awakens' the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread.
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injectable Bioresponsive gel depot for enhanced immune checkpoint blockade
Advanced Materials, 2018Co-Authors: Chao Wang, Yuqi Zhang, Jinqiang Wang, Xudong Zhang, Wujin Sun, Xuesi ChenAbstract:Although cancer immunotherapy based on immune checkpoint inhibitors holds great promise toward many types of cancers, several challenges still remain, associated with low objective response of patient rate as well as systemic side effects. Here, a combination immunotherapy strategy is developed based on a thermogelling reactive oxygen species (ROS)-responsive polypeptide gel for sustained release of anti-programmed cell death-ligand 1 antibody and dextro-1-methyl tryptophan, inhibitor of indoleamine-2,3-dioxygenase with leveraging the ROS level in the tumor microenvironment. This Bioresponsive gel depot can effectively reduce the local ROS level and facilitate release of immunotherapeutics, which leads to enhanced anti-melanoma efficacy in vivo.
Guojun Chen - One of the best experts on this subject based on the ideXlab platform.
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Bioresponsive protein complex of apd1 and acd47 antibodies for enhanced immunotherapy
Nano Letters, 2019Co-Authors: Jinqiang Wang, Xudong Zhang, Qian Chen, Guojun Chen, Jiawen Chen, Jingjing Shen, Amanda ChanAbstract:Despite the promising efficacy of immune checkpoint blockade (ICB) in treating many types of cancers, the clinical benefits have often been restricted by the low objective response rates and systemic immune-related adverse events. Here, a Bioresponsive ICB treatment is developed based on the reactive oxygen species (ROS)-sensitive protein complex for controlled sequential release of anti- "don't eat me" signal antibody (aCD47) and antiprogrammed cell death protein 1 (aPD1), by leveraging the abundant ROS in the tumor microenvironment (TME). These protein complexes can also act as scavengers of ROS in the TME to reverse the immunosuppressive responses, thereby enhancing antitumor efficacy in vivo. In a melanoma cancer model, the synergistic antitumor efficacy was achieved, which was accompanied by enhanced T cell immune responses together with reduced immunosuppressive responses.
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a dual Bioresponsive drug delivery depot for combination of epigenetic modulation and immune checkpoint blockade
Advanced Materials, 2019Co-Authors: Huitong Ruan, Jinqiang Wang, Qian Chen, Guojun Chen, Di Wen, Hao ChengAbstract:Patients with advanced melanoma that is of low tumor-associated antigen (TAA) expression often respond poorly to PD-1/PD-L1 blockade therapy. Epigenetic modulators, such as hypomethylation agents (HMAs), can enhance the antitumor immune response by inducing TAA expression. Here, a dual Bioresponsive gel depot that can respond to the acidic pH and reactive oxygen species (ROS) within the tumor microenvironment (TME) for codelivery of anti-PD1 antibody (aPD1) and Zebularine (Zeb), an HMA, is engineered. aPD1 is first loaded into pH-sensitive calcium carbonate nanoparticles (CaCO3 NPs), which are then encapsulated in the ROS-responsive hydrogel together with Zeb (Zeb-aPD1-NPs-Gel). It is demonstrated that this combination therapy increases the immunogenicity of cancer cells, and also plays roles in reversing immunosuppressive TME, which contributes to inhibiting the tumor growth and prolonging the survival time of B16F10-melanoma-bearing mice.
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in situ sprayed Bioresponsive immunotherapeutic gel for post surgical cancer treatment
Nature Nanotechnology, 2019Co-Authors: Yuqi Zhang, Chao Wang, Jinqiang Wang, Xudong Zhang, Qian Chen, Guojun Chen, Di Wen, Guang Yang, Chen JiangAbstract:Cancer recurrence after surgical resection remains a significant cause of treatment failure. Here, we have developed an in situ formed immunotherapeutic Bioresponsive gel that controls both local tumour recurrence after surgery and development of distant tumours. Briefly, calcium carbonate nanoparticles pre-loaded with the anti-CD47 antibody are encapsulated in the fibrin gel and scavenge H+ in the surgical wound, allowing polarization of tumour-associated macrophages to the M1-like phenotype. The released anti-CD47 antibody blocks the 'don't eat me' signal in cancer cells, thereby increasing phagocytosis of cancer cells by macrophages. Macrophages can promote effective antigen presentation and initiate T cell mediated immune responses that control tumour growth. Our findings indicate that the immunotherapeutic fibrin gel 'awakens' the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread.