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金纳米棒辅助光热疗法治疗小鼠膀胱癌:关于金纳米棒在膀胱癌中心、周边和表面分布影响的计算研究。

Gold nanorods assisted photothermal therapy of bladder cancer in mice: A computational study on the effects of gold nanorods distribution at the centre, periphery, and surface of bladder cancer.

作者信息

Cheong Jason Kk, Ooi Ean H, Chiew Yeong S, Menichetti Luca, Armanetti Paolo, Franchini Mauro Comes, Alchera Elisa, Locatelli Irene, Canu Tamara, Maturi Mirko, Popov Viktor, Alfano Massimo

机构信息

Ascend Technologies Ltd, Wessex House, Upper Market Street, Eastleigh, SO50 9FD, United Kingdom; Mechanical Engineering Discipline, School of Engineering and Advanced Engineering Platform, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Malaysia.

Ascend Technologies Ltd, Wessex House, Upper Market Street, Eastleigh, SO50 9FD, United Kingdom; Mechanical Engineering Discipline, School of Engineering and Advanced Engineering Platform, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Malaysia.

出版信息

Comput Methods Programs Biomed. 2023 Mar;230:107363. doi: 10.1016/j.cmpb.2023.107363. Epub 2023 Jan 21.

Abstract

BACKGROUND AND OBJECTIVES

Gold nanorod-assisted photothermal therapy (GNR-PTT) is a cancer treatment whereby GNRs incorporated into the tumour act as photo-absorbers to elevate the thermal destruction effect. In the case of bladder, there are few possible routes to target the tumour with GNRs, namely peri/intra-tumoural injection and intravesical instillation of GNRs. These two approaches lead to different GNR distribution inside the tumour and can affect the treatment outcome.

METHODOLOGY

The present study investigates the effects of heterogeneous GNR distribution in a typical setup of GNR-PTT. Three cases were considered. Case 1 considered the GNRs at the tumour centre, while Case 2 represents a hypothetical scenario where GNRs are distributed at the tumour periphery; these two cases represent intratumoural accumulation with different degree of GNR spread inside the tumour. Case 3 is achieved when GNRs target the exposed tumoural surface that is invading the bladder wall, when they are delivered by intravesical instillation.

RESULTS

Results indicate that for a laser power of 0.6 W and GNR volume fraction of 0.01%, Case 2 and 3 were successful in achieving complete tumour eradication after 330 and 470 s of laser irradiation, respectively. Case 1 failed to form complete tumour damage when the GNRs are concentrated at the tumour centre but managed to produce complete tumour damage if the spread of GNRs is wider. Results from Case 2 also demonstrated a different heating profile from Case 1, suggesting that thermal ablation during GNR-PTT is dependant on the GNRs distribution inside the tumour. Case 3 shows similar results to Case 2 whereby gradual but uniform heating is observed. Cases 2 and 3 show that uniformly heating the tumour can reduce damage to the surrounding tissues.

CONCLUSIONS

Different GNR distribution associated with the different methods of introducing GNRs to the bladder during GNR-PTT affect the treatment outcome of bladder cancer in mice. Insufficient spreading during intratumoural injection of GNRs can render the treatment ineffective, while administered via intravesical instillation. GNR distribution achieved through intravesical instillation present some advantages over intratumoural injection and is worthy of further exploration.

摘要

背景与目的

金纳米棒辅助光热疗法(GNR-PTT)是一种癌症治疗方法,其中注入肿瘤的金纳米棒充当光吸收剂,以增强热破坏效果。对于膀胱癌而言,用金纳米棒靶向肿瘤的途径有限,即瘤周/瘤内注射和膀胱内灌注金纳米棒。这两种方法会导致金纳米棒在肿瘤内的分布不同,进而可能影响治疗效果。

方法

本研究在GNR-PTT的典型设置中研究了金纳米棒不均匀分布的影响。考虑了三种情况。情况1考虑金纳米棒位于肿瘤中心,而情况2代表一种假设情况,即金纳米棒分布在肿瘤周边;这两种情况代表肿瘤内积聚,金纳米棒在肿瘤内的扩散程度不同。情况3是通过膀胱内灌注使金纳米棒靶向侵入膀胱壁的暴露肿瘤表面时实现的。

结果

结果表明,对于0.6W的激光功率和0.01%的金纳米棒体积分数,情况2和情况3分别在激光照射330秒和470秒后成功实现了肿瘤的完全根除。当金纳米棒集中在肿瘤中心时,情况1未能形成完全的肿瘤损伤,但如果金纳米棒的扩散范围更广,则能够产生完全的肿瘤损伤。情况2的结果也显示出与情况1不同的加热曲线,这表明GNR-PTT期间的热消融取决于金纳米棒在肿瘤内的分布。情况3显示出与情况2相似的结果,即观察到逐渐但均匀的加热。情况2和情况3表明,均匀加热肿瘤可以减少对周围组织的损伤。

结论

在GNR-PTT期间,与将金纳米棒引入膀胱癌的不同方法相关的不同金纳米棒分布会影响小鼠膀胱癌的治疗效果。瘤内注射金纳米棒时扩散不足可能导致治疗无效,而通过膀胱内灌注给药。通过膀胱内灌注实现的金纳米棒分布比瘤内注射具有一些优势,值得进一步探索。

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