Cancer is currently the most significant risk to human well-being worldwide. Global cancer data show that 24% of deaths in China are attributable to the disease, and rising healthcare costs and patient populations mean that the country now spends over 220 billion yuan annually on cancer treatment. Therapeutic drug administration (chemotherapy) has a substantial impact on most cancers [1] . Chemotherapy is one of the most successful cancer treatments, and it has vastly increased patient survival rates and enhanced their quality of life [2]. However, most anticancer treatments are broad-spectrum drugs with significant toxic and side effects that can lead to drug resistance and severe damage to patients' bodily functions [3]. Accordingly, there has been a recent interest in developing better anticancer drugs despite their poor water solubility, imprecise absorption in vivo, and low bioavailability [[4], [5], [6]].

Photothermal treatment is a promising cancer therapeutic application because of its low invasiveness, high precision, and remarkable selectivity [[7], [8], [9]]. Nanoparticles are often utilized as photothermal agents in PTT because of their specific features, with high photothermal efficacy and tiny diameters that permit tumor penetration [10]. It is possible to tailor the photothermal agent's electrical, optical, and mechanical properties by adjusting the nanoparticle composite structure, shape, and size. As a result of their exceptional photothermal properties, noble metal nanoparticles have recently attracted a lot of interest for application in PTT. The special SPR effect of creating heat by laser absorbing energy has proved promising for PTT with noble metal nanoparticles [11]. In addition, they have excellent radioactive scattering properties, which opens the door to various modalities, such as imaging-guided PTT. AuNPs provide high biocompatibility, biological conjugation chemistry, the opportunity to conjugate with drugs via Au-thiol, high yield, smooth synthesis, and surface functionalization-controlled PTT mediator [12]. It is possible to synthesize AuNPs in various sizes and shapes, such as spheres, cages, shells, and rods. There is a surface plasmon resonance (SPR) effect, and their radioactivity has been enhanced. Different shaped AuNPs have unique features that could make them useful in various PTT approaches to cancer therapy [13]. Changing the size and shape of AuNPs can affect their photochemical activities linked to local surface plasmon resonance (LSPR) [14]. This allows them to be used at a wide range of light wavelengths by adjusting their photoacoustic and photothermal properties. In addition, using AuNPs enables the material to be distributed systemically, explicitly targeted to tumors, and excreted harmlessly in the urine [15]. Biocompatibility, the possibility of tumor penetration following systemic delivery due to their small size, and the chance of binding to the drugs of gold-thiol conjugation. This has led scientists to suggest that AuNPs could be a useful PTT agent in breast cancer treatment [16].

D-glycosidic bonds link d-glucuronic acid and N-acetyl-D-glucosamine to form Hyaluronic acid (HA), a negatively charged polysaccharide. Because of its biodistribution, reactive oxygen species (ROS) and hyaluronidase (HAase) in vivo can destroy HA at varying rates, making it a vital factor of the extracellular matrix (ECM) with great biocompatibility. Scaffolds made from HA are commonly employed in tissue repair, regeneration, and engineering [17]. Drugs could be released from HA-drug delivery systems (DDSs) for tumor therapy by capitalizing on the distinct tumor microenvironment (TME), which overexpressed HAase. HA has many functional groups, such as hydroxyl and carboxyl. When sodium periodate is used to oxidize HA, aldehyde groups are generated [18]. Adipic dihydrazide can be coupled with HA to generate amino groups. Stimuli-responsive linkers, lipophilic moieties, antibodies, probes, and drugs are all examples of molecules that can be attached to HA through its aldehydes and amino groups. Toll-like receptor 4 (TLR-4), the receptor for HA-mediated motility (RHAMM), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) are some of the receptors that HA has been shown to bind to precisely [19]. Among these receptors, the interaction between CD44 and HA is most widely employed for building DDSs since overexpressed CD44 on the surface of various tumor cells and cells concerned with inflammatory disorders. In addition to its biocompatibility and CD44-targeting feature, HA's abundance as a natural polymer makes it potentially more accessible to get than synthetic polymers that need many chemical steps [[20], [21], [22]].

Reducing the size of a tumor while using the widely used taxane derivatives paclitaxel and docetaxel has been shown to increase survival rates for cancer patients. Drug resistance develops when they are constantly exposed to patients, diminishing the treatment's efficacy [23]. Cabazitaxel (CZT), a more recent semisynthetic derivative of taxanes, displays less drug resistance in cancer patients; it was approved by the FDA in 2010. CZT's anticancer effect relies on blocking microtubule disintegration in the same way as other taxanes [24]. Being less p-glycoprotein-binding than paclitaxel and docetaxel, it can be used as a taxane substitute or in patients who have developed resistance to taxanes. The fundamental goal of the targeted drug delivery system is to deliver the necessary anticancer drugs directly to the tumor microenvironment [25]. Active and passive targeting are two techniques for drug delivery that may be utilized to reduce the dose-dependent toxicities of anticancer drugs. Nanomedicines with a particle size of 200 nm that are circulating in the blood might concentrate in tumor vessels thanks to the enhanced permeability and retention (EPR) effect, which occurs because tumor vessels are characterized by extravasation [[26], [27], [28]]. The EPR phenomenon allows nanomedicine to accumulate at the tumor site, making this a passive targeting method. Furthermore, cancer-specific targeting ligands are anchored on the surface of the nanomedicine in the active targeting technique for targeted internalization in cancer cells [29].

In the investigation, we developed a drug delivery system (HA/Au-PDA@CZT) that targets tumors and responds to light and heat for combined chemo-photothermal treatment. The LSPR peak red-shifted in the NIR range demonstrated by the nanoplatform gave it an enhanced photothermal conversion ability. In conjunction with CZT treatment, PTT caused by HA/Au-PDA@CZT under NIR laser irradiation can potentially increase tumor therapeutic impact while decreasing adverse effects (Fig. 1). The multifunctional nanomedicine showed significant tumor suppression in vitro and in vivo investigations.