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Intelligent delivery system targeting PD-1/PD-L1 pathway for cancer immunotherapy
Ning Liu1, Renshuai Zhang1, Qiang Shi2
1The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China; Cancer Institute, Qingdao University, Qingdao 266071, China.
Abstract:
The drugs targeting the PD-1/PD-L1 pathway have gained abundant clinical applications for cancer immunotherapy. However, only a part of patients benefit from such immunotherapy. Thus, brilliant novel tactic to increase the response rate of patients is on the agenda. Nanocarriers, particularly the rationally designed intelligent delivery systems with controllable therapeutic agent release ability and improved tumor targeting capacity, are firmly recommended. In light of this, state-of-the-art nanocarriers that are responsive to tumor-specific microenvironments (internal stimuli, including tumor acidic microenvironment, high level of GSH and ROS, specifically upregulated enzymes) or external stimuli (e.g., light, ultrasound, radiation) and release the target immunomodulators at tumor sites feature the advantages of increased anti-tumor potency but decreased off-target toxicity. Given the fantastic past achievements and the rapid developments in this field, the future is promising. In this review, intelligent delivery platforms targeting the PD-1/PD-L1 axis are attentively appraised. Specifically, mechanisms of the action of these stimuli-responsive drug release platforms are summarized to raise some guidelines for prior PD-1/PD-L1-based nanocarrier designs. Finally, the conclusion and outlook in intelligent delivery system targeting PD-1/PD-L1 pathway for cancer immunotherapy are outlined.
Insights
Intelligent nanocarriers enhance cancer immunotherapy by targeting the PD-1/PD-L1 pathway. These stimuli-responsive systems improve drug delivery to tumors, increasing efficacy and reducing side effects for better patient outcomes.
Area of Science:
- Oncology
- Nanotechnology
- Immunotherapy
Background:
- Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway are crucial in cancer immunotherapy.
- Current limitations include a subset of patients who do not respond to these therapies, necessitating novel strategies.
- Intelligent nanocarriers offer a promising approach to overcome these limitations.
Purpose of the Study:
- To review advanced nanocarrier systems designed for targeted delivery of immunomodulators against the PD-1/PD-L1 axis.
- To explore stimuli-responsive nanocarriers that release therapeutic agents in tumor-specific microenvironments or upon external triggers.
- To provide guidelines for designing future nanocarrier-based immunotherapies.
Main Methods:
- Literature review of recent advancements in intelligent nanocarriers for cancer immunotherapy.
- Analysis of nanocarrier designs responsive to internal tumor stimuli (e.g., pH, GSH, enzymes) and external stimuli (e.g., light, ultrasound).
- Summarization of mechanisms underlying stimuli-responsive drug release for enhanced anti-tumor activity.
Main Results:
- Intelligent nanocarriers demonstrate improved tumor targeting and controlled release of immunomodulators.
- Stimuli-responsive systems effectively increase anti-tumor potency while minimizing off-target toxicity.
- These platforms show significant potential for enhancing the efficacy of PD-1/PD-L1-based cancer immunotherapy.
Conclusions:
- Intelligent nanocarriers represent a significant advancement in cancer immunotherapy by optimizing PD-1/PD-L1 targeting.
- Stimuli-responsive drug delivery systems are key to improving treatment response rates and reducing adverse effects.
- The future development of these nanocarriers holds great promise for personalized cancer treatment.
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