Photothermal nanoparticles delivering heat-triggered siRNA for tumor therapy - Letter to the Editor

Sep 29, 2026

Uploaded by kopisore

Letter to the Editor discusses the limitations of conventional chemotherapy, including poor tumor penetration, systemic toxicity, and emerging resistance. It highlights photothermal therapy (PTT) combined with RNA interference as an alternative, focusing on heat-shock protein (HSP) silencing using heat-triggered siRNA-loaded nanoparticles. The text summarizes preclinical evidence showing improved tumor regression and gene silencing, while also noting challenges in heterogeneous nanoparticle distribution, temperature control, and the need for long-term safety, biodegradation, and pharmacokinetic studies before clinical translation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages2

Reading Time5 min

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Letter to the Editor

Background: chemotherapy limitations

PTT with RNA interference and HSP targeting

Heat-triggered siRNA nanoparticle design

Preclinical evidence

Remaining challenges and outlook

Letter to the Editor Photothermal nanoparticles delivering heat-triggered siRNA for tumor therapy Fahad Amin, MBBSa , Ayesha Imran, MBBSb , Raghabendra Kumar Mahato, MBBSc ,* To the Editor, Treating cancer remains a dilemma in medicine even today. Conventional chemotherapy remains a cornerstone of cancer treatment, but its effectiveness is often limited. Limitations include poor tumor penetration, systemic toxicity, and damage to healthy tissues[1] . Tumors located deep within the body or surrounded by dense vasculature may be particularly resistant to chemotherapeutic agents. Moreover, the cancer cells can develop mechanisms of resistance over time, reducing longterm treatment efficacy. These challenges have motivated the scientists to develop alternative strategies to treat carcinomas. Photothermal therapy (PTT) combined with RNA interference is one such modality. PTT involves localized heating to kill the tumor cells. However, the major limitation of this type of therapy is the activation of heat-shock proteins (HSPs) within cancer cells. These proteins enhance survival and may lead to developing resistance to thermal stress[2]. To overcome this problem, researchers have developed some special small interfering RNA (siRNA) that is delivered via nanoparticles. These siRNA molecules can specifically silence genes encoding HSPs, which makes tumor cells more susceptible to thermal damage while sparing healthy tissue. Heat-triggered siRNA nanoparticles are designed to release their cargo selectively in response to the elevated temperatures produced by PTT. This makes sure that siRNA acts predominantly within the tumor microenvironment that minimizes offtarget effects and improves therapeutic precision. Nanoparticles can be designed from various materials such as gold nanorods, human serum albumin, and other biocompatible carriers. Preclinical studies have demonstrated the efficacy of this approach in this regard. In murine breast tumor models gold aFaculty of Medicine, King Edward Medical University, Pakistan, bDepartment of Medicine, King Edward Medical University, Lahore, Pakistan and cDepartment of Medicine, Gandaki Medical College Teaching Hospital and Research Center, Pokhara, Nepal Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. All authors agreed and approved for final submission. *Corresponding author. Address: Department of Medicine, Gandaki Medical College Teaching Hospital and Research Center, Pokhara 33700, Nepal. Tel.: +977-9745829807. E-mail: [102raghabendrakumarmahato@gmail.com](102raghabendrakumarmahato@gmail.com)[ ](102raghabendrakumarmahato@gmail.com)(R. K. Mahato). Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons AttributionNon Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Annals of Medicine & Surgery (2026) 88:1148–1149 Received 21 November 2025; Accepted 2 December 2025 Published online 12 December 2025 [http://dx.doi.org/10.1097/MS9.0000000000004580](http://dx.doi.org/10.1097/MS9.0000000000004580) nanorods carrying HSP-70 siRNA showed significantly greater tumor regression when combined with heat than heat treatment alone[3]. Similarly the albumin-based nanoparticles delivering both siRNA and imaging dyes enabled in vitro and in vivo heat-triggered gene silencing and tumor inhibition[4]. Another study in cancerous colonic cell confirmed that siRNA delivery during PTT increased apoptosis and reduced HSP expression[5]. Despite these promising results, several challenges remain. Distribution of the nanoparticles within tumors is of heterogeneous nature. This can limit effective heat delivery and siRNA silencing in all tumor re

FAQs

Why is conventional chemotherapy often limited for tumor treatment?

It can suffer from poor tumor penetration, systemic toxicity, and damage to healthy tissues. Tumors may also develop resistance over time, reducing long-term efficacy.

How does photothermal therapy work when combined with siRNA?

PTT uses localized heating to kill tumor cells, while siRNA specifically silences genes encoding heat-shock proteins. Releasing siRNA in response to elevated temperatures helps action occur mainly in the tumor microenvironment.

What challenges must be solved before this approach can be used clinically?

Nanoparticle distribution in tumors is heterogeneous, which can limit effective delivery and silencing. Precise temperature control is also required to avoid collateral damage, and long-term safety, biodegradation, and pharmacokinetics need further study.

Sep 29, 2026

Uploaded by kopisore