Tumor‐Activated Size‐Enlargeable Bioinspired Lipoproteins Access Cancer Cells in Tumor to Elicit Anti‐Tumor Immune Responses

Abstract

The limited lymphocytes infiltration and immunosuppression in tumor are the major challenges of cancer immunotherapy. The use of immunogenic cell death (ICD)‐inducing agents has potential to potentiate antitumor immune responses, but is tremendously hampered by the poor delivery efficiency. Herein, a tumor‐activated size‐enlargeable bioinspired lipoprotein of oxaliplatin (TA‐OBL) is designed to access cancer cells and boost the ICD‐induced antitumor immunity for synergizing immune‐checkpoint blockades (ICBs)‐mediated immunotherapy. TA‐OBL is constructed by integrating a legumain‐sensitive melittin conjugate for improving intratumoral permeation and cancer cell accessibility, a pH‐sensitive phospholipid for triggering size‐enlargement and drug release in intracellular acidic environments, a nitroreductase‐sensitive hydrophobic oxaliplatin prodrug (N‐OXP) for eliciting antitumor immunity into the bioinspired nano‐sized lipoprotein system. TA‐OBL treatment produced robust antitumor immune responses and its combination with ICBs demonstrates strong therapeutic benefits with delayed tumor growth and extended survival rate, making it a promising delivery nanoplatform to elicit antitumor immunity for cancer immunotherapy.

Multifunctional metal-organic framework-based nanoreactor for starvation/oxidation improved indoleamine 2,3-dioxygenase-blockade tumor immunotherapy

“…3a and Supplementary Fig. 1a , Mn-DTA exhibits a spherical structure with a size of ~50 nm, which is beneficial for overcoming biobarriers of high interstitial pressure and dense tumor extracellular matrix, leading to a superior tumor penetration and an improved delivery efficiency 22 , 23 . The structure of Mn-DTA was further verified by energy-dispersive X-ray spectroscopy (EDS) elemental mappings of Mn, S and O (Fig.…”

Targeting ferroptosis-based cancer therapy using nanomaterials: strategies and applications

“…The approach to achieve synergistic anti-PD-L1 immunotherapy has been developed. For example, the nano platform developed by Li et al ., which can enlarge LIP and enhance the function of CD8 + T cells and their intratumoral infiltration as well as synergize with immunotherapy 64 .…”

Platinum-Induced Peripheral Neuropathy (PIPN): ROS-Related Mechanism, Therapeutic Agents, and Nanosystems

“…Pt prodrugs have attracted wide attention because they present low toxicity in normal tissues and can be activated by stimulus to release cytotoxic Pt drugs. Up to now, various types of endogenous/exogenous stimulus-sensitive Pt prodrugs have been reported, such as pH-sensitive ( Feng et al, 2018 ), ROS-sensitive ( Feng et al, 2019 ), light-sensitive ( He et al, 2018 ), and nitroreductase-sensitive prodrugs ( Li et al, 2020 ). For example, Feng et al synthesized PEGylated OXA prodrug (DiPt-TK-PEG 2K ) via a ROS-liable thioketal spacer and assembled them with reduction-responsive heterodimer of photosensitizer pheophorbide A (PPa) and indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor (NLG919) ( Figure 2A ).…”