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Page 2 of 17 Sun et al. Chem Synth 2023;3:16 https://dx.doi.org/10.20517/cs.2022.45

INTRODUCTION
Cancer, as one of the most malignant diseases, has become a serious threat to global public health .
[1,2]
Currently, the common clinical modalities of cancer treatment are surgery, chemotherapy and radiotherapy.
Though demonstrated to be effective, all of the above methods have drawbacks . Surgery can cause
[3-6]
[7]
unpleasant pain to patients and unavoidably, induce cancer metastasis . Chemotherapy and radiotherapy
are well known to have side effects and, additionally, cause undesired drug resistance . Therefore, the
[8]
development of novel approaches to cancer treatment is still urgent.

Photothermal cancer therapy is a therapeutic modality that converts near-infrared (NIR) photon energy
into heat and, subsequently, initiates the apoptosis of cancer cells through hyperthermia [9-11] . Due to the high
selectivity, spatiotemporal control, negligible drug resistance, etc. [12-14] , photothermal therapy has attracted
much attention in the last few decades and is regarded as a promising approach to cancer treatment. In
order for photothermal therapy to achieve satisfactory therapeutic effects and low side effects, several factors
need to be taken into consideration for the design of photothermal agents. Firstly, high photothermal
conversion efficiency ensures the initiation of hyperthermia and remains to be one of the most important
parameters for the evaluation of photothermal agents. Secondly, the sufficient accumulation and
distribution of photothermal agents at tumor sites not only guarantee the targeted therapy but also reduce
the possible side effect, which makes them attractive factors that have attracted much attention. Thirdly, the
combination of photothermal therapy with other therapeutic modalities (e.g., chemotherapy, photodynamic
therapy, gene therapy) offers synergistic enhancement of anticancer effect and serves as an alternative
strategy for the further optimization of photothermal therapy.

Host-guest assemblies, with the inclusion of small molecular guests into the cavity of macrocyclic hosts, are
attractive to supramolecular chemists. They can be constructed via the manipulation of the size and non-
covalent interactions (e.g., hydrogen bonding, electrostatic interaction, - interaction, hydrophobic
interaction) between host and guest [15-18] . Due to their easy design, morphological diversity, stimuli-
responsive property, etc., the host-guest assemblies have been broadly applied in the field of
chemosensing [19,20] , catalysis [21,22] and bio-applications [23-26] . Particularly, in the area of photothermal therapy,
the host-guest assemblies show multiple advantages and significantly promote the improvement of cancer
treatment. However, the related endeavors have not been systematically summarized and discussed. Thus,
in this review, to benefit the design of advanced host-guest assembly-based photothermal agents and
promote the further development of photothermal therapy, the major achievements that the host-guest
assemblies have made in the field of photothermal therapy [Scheme 1], including the enhancement of
photothermal conversion efficiency, the improvement of targeted distribution at tumor sites, and the
superiority of constructing photothermal-derived multimodal synergistic therapy, are mainly discussed.
Additionally, the future perspectives of host-guest assemblies-based photothermal therapy are envisioned.
Overall, the review clarifies the unique function of host-guest assemblies in photothermal therapy and, more
importantly, provides guidance for the development of host-guest assemblies-based cutting-edge
photothermal therapeutic modality.

HOST-GUEST INTERACTION-ACTUATED ENHANCEMENT OF PHOTOTHERMAL
CONVERSION EFFICIENCY
Though photothermal therapy has attracted much attention, the insufficient photothermal conversion
efficiency in NIR range remains an obstacle to its clinical application [27,28] . Therefore, the optimization of the
photothermal agents in this aspect is emerging as an appealing research direction. In addition, the NIR light
employed for photothermal therapy is mostly limited to NIR-I (750-1,000 nm) [29-32] . However, compared
with NIR-I, NIR-II (1,000-1,350 nm) is featured with larger penetration depth and maximum permissible