1. Introduction
In recent decades, precision therapy
has emerged as a prominent approach in clinical cancer treatment.
Alongside traditional methods such as surgery, chemotherapy, and
radiotherapy, novel treatments like targeted therapy, interventional
therapy, and immunotherapy have expanded the options available to
healthcare professionals.[1-5] A promising development in cancer
treatment is photothermal therapy (PTT), which is a non-invasive and
highly targeted treatment method.[6-10] When exposed to an external
light source, the photothermal agents (PTAs) injected and accumulated in
lesion tissues will convert light energy into heat energy to effectively
kill the diseased cells such as tumor cells. PTT offers several
advantages, including high selectivity, minimal systemic toxic side
effects, short treatment durations (typically just a few minutes), and
noticeable therapeutic effects. Conventional PTT often requires high
local temperatures exceed 50 ℃, which may also inadvertently damage
surrounding healthy tissue, leading to challenges in achieving optimal
treatment outcomes.[11-14] Besides, the suboptimal effectiveness of
conventional PTT can be attributed to various factors including
heterogeneous PTA distribution (PTAs may not be evenly distributed
within cancer cells), limited light penetration (The depth to which the
laser light can penetrate is restricted, making it less effective for
deep-seated tumors), and difficulty in temperature control (Precisely
controlling the photothermal process is challenging and may lead to
overheating, causing severe side effects, including inflammation, immune
system evasion, metastasis, and harm to normal tissues surrounding the
tumor).
To address these shortcomings, researchers have been exploring the
potential of mild PTT (MPTT, operating at lower temperatures, typically
below 45 ℃), which has the potential to significantly improve treatment
efficacy, reduce drug dosage, lower hyperthermia temperatures, and
minimize damage to healthy tissues.[15-18] In cancer therapy, one
avenue of research involves inhibiting the synthesis of
heat shock proteins (HSPs) in tumor
cells, which help to develop heat resistance.[19-21] By blocking
HSPs expression, MPTT can kill tumor cells at lower temperatures without
harming nearby healthy cells. Despite significant progress in MPTT, it
remains primarily in the stages of basic and clinical research, and has
not yet seen widespread clinical adoption due to several technical
challenges. For instance, striking the right balance between
hyperthermia and MPTT temperatures is crucial to avoid damaging normal
tissues while maintaining treatment effectiveness. Besides, current
clinical lasers have limited penetration depth, restricting their use to
superficial tumors.[22-25] Therefore, choosing the suitable
near-infrared (NIR) PTAs is significant for various biomedical
applications, as some organic molecules have limited photothermal
stability, while inorganic nanomaterials may pose potential toxicity
risks.
In this review, we provide a
comprehensive overview of the recent development of MPTT, emphasizing
its mechanisms, the characteristics of commonly used NIR PTAs (both
organic and inorganic materials), and the applications in biomedicine
field (Scheme 1). Then, we address the key obstacles facing MPTT and
propose the potential solutions, and explore the status of MPTT combined
with other anti-tumor therapies. Specifically, we discuss the broader
applications in areas such as anti-infection, obesity treatment, and
vascular disease treatment. Finally, we look ahead to future research
directions in MPTT, aiming to enhance its efficiency and safety while
developing new strategies for high-efficiency MPTT.