In–Situ‐Sprayed Dual‐Functional Immunotherapeutic Gel for Colorectal Cancer Postsurgical Treatment

Abstract

Surgery remains the most preferred treatment options for colorectal cancer (CRC). Paradoxically, local recurrence and distant metastasis are usually accelerated postsurgery as a consequence of local and systemic immunosuppression caused by surgery. Therefore, modulating tumor postoperative immune microenvironment and activating systemic antitumor immunity are necessary supplementaries for CRC therapy. Here, an in-situ-sprayed immunotherapeutic gel loaded with anti-OX40 antibody (iSGels@aOX40) is reported for CRC postsurgical treatment. The iSGel is formed instantly after spraying with strong adhesion ability via crosslinking between tannic acid (TA) and poly(l-glutamic acid)-g-methoxy poly(ethylene glycol)/phenyl boronic acid (PLG-g-mPEG/PBA). TA not only serves as one component of the iSGel but also relieves the postsurgical immunosuppressive microenvironment by inhibiting the activity of cyclo-oxygenase-2 (COX-2). The aOX40 serves as an immune agonistic antibody and is released from the iSGel in a constant manner lasting for over 20 days. In a subcutaneous murine CRC model, the iSGels@aOX40 results in complete inhibition on tumor recurrence. In addition, the cured mice show resistance to tumor re-challenge, suggesting that immune memory effects are established after the iSGels@aOX40 treatment. In an orthotopic CRC peritoneal metastatic model, the iSGels@aOX40 also remarkably inhibits the growth of the abdominal metastatic tumors, suggesting great potential for clinical CRC therapy.

Clinical Characteristics of Bloodstream Infection in Immunosuppressed Patients: A 5-Year Retrospective Cohort Study

“…Generally, typical immunosuppressive status includes patients with hematological diseases, tumor, oral immunosuppressive medications, solid-organ transplant, stem cell transplant, or bone marrow transplant, and atypical immunosuppressive status includes patients with diabetes mellitus, liver cirrhosis, and burns ( Mylotte and Tayara, 2000 ; Li et al., 2021 ; Willis et al., 2021 ). Studies revealed that immunosuppression could result from critical surgery as well ( Si et al., 2021 ), and sometimes postoperative patients are susceptible to infections caused by opportunistic pathogens ( Mada et al., 2020 ; Shipman et al., 2021 ). IS patients with infections may present with atypical signs and symptoms.…”

Stretchable and Skin‐Attachable Electronic Device for Remotely Controlled Wearable Cancer Therapy

“…In female black mice, B16F10 melanoma tumors are established in armpits and then surgically debulked by ≈2/3 to simulate nonideal surgical conditions. [ 22 ] The mice are randomly divided into four groups, including i) the control group (without treatment), ii) the TPU nanotextile dressing containing free DOX group, iii) the wearable electro‐thermal therapy (ETT) group, and iv) the wearable combined therapy group. The stretchable electronic patch is conformally attached to the surgical wound site with abundant exudate for wearable treatments, as shown in Figure S21 (Supporting Information).…”

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

“…In the implant group, the residual tumors were eradicated after surgery, which helped inhibit distal tumor metastasis and induced immune-memory effects resisting the re-challenge experiment. Recently, Si et al [ 21 ] further improved a nanogel implant to an in-situ -sprayed gel delivering anti-OX40 antibody, which demonstrated the promising therapeutic potential of CRC. This improved nanogel modulated the suppressive immune microenvironment by inhibiting the activity of cyclo-oxygenase-2 (COX-2); as a result, the loaded aOX40 was gradually released for over 20 days, serving as an immune agonistic antibody.…”