Upper-Critical-Solution-Temperature Polymer Modified Gold Nanorods for Laser Controlled Drug Release and Enhanced Anti-Tumour Therapy

Abstract

Photothermal therapy (PTT) has become effective method for the treatment of malignant cancer. The development of PTT system with high anti-tumour effect is still the feasible research direction. Here, a new type of gold nanorods (AuNRs)-doxorubicin (DOX)/mPEG10K-peptide/P(AAm-co-AN) (APP-DOX) nano drug delivery system was proposed. Among them, AuNRs was used as high-efficiency photothermal agent. APP-DOX had a suitable size and can be targeted to accumulate in tumour tissues through circulation in the body. The abundant matrix metalloproteinase 2 (MMP-2) in the tumour environment intercepted and cut off the short peptide chain structure grafted on APP-DOX. At the same time, the removal of the PEG segment leaded to an increase in the hydrophobic properties of the system. Nanoparticles aggregated into large particles, causing them to stay and aggregate further at the tumour site. When irradiated by 808 nm near-infrared laser, APP-DOX achieved a gradual heating process. High temperature can effectively ablate tumours and enable UCST polymer to achieve phase transition, resulting in more anti-cancer drugs loaded in the polymer layer DOX was released, effectively killing cancer cells. Animal experiments had verified the possibility of the nano drug-carrying system and good tumour treatment effect. What’s more worth mentioning is that compared with free DOX, the nano drug delivery system had lower biological toxicity and not cause obvious harmful effects on normal organs and tissues.

Synergistic Approaches in the Design and Applications of UCST Polymers

“…[ 97 ] Similarly, controlled release of DOX can also be achieved with P(Am‐co‐AN). [ 98,99 ] Yang et al. reported a size‐shrinkable P(Am‐ co ‐AN)‐ g ‐PEG‐Lipoic acid (LA) micelles loaded with gold nanorods (AuNRs) and DOX for photothermal‐chemotherapy (Figure 6b).…”

“…[97] Similarly, controlled release of DOX can also be achieved with P(Am-co-AN). [98,99] Yang et al reported a size-shrinkable P(Am-co-AN)-g-PEG-Lipoic acid (LA) micelles loaded with gold nanorods (AuNRs) and DOX for photothermal-chemotherapy (Figure 6b). [100] The AuNRs at the tumor site converted the light energy into heat, and the nanomicelles were split into a cascade of ultra-small micelles simultaneously.…”

Metal-Polymer Nanoconjugates Application in Cancer Imaging and Therapy

“…The former is often explored to enhance the quantum efficiency and photostability of fluorophores, allowing the detection of lower quantities of biomarkers used in biosensing or bioimaging [32]. The latter is the foundation stone for the application of metallic nanoparticles in cancer hyperthermia/photothermal therapy [33]. However, it is essential to tailor the nanomaterials to interact specifically with near-infrared (NIR) radiation, a region of the spectra where the major biological components (e.g., collagen, hemoglobin, and water) have the lowest or insignificant absorption [34].…”

“…The higher blood circulation times associated with the utilization of these polymers will increase the nanomaterials' probability to accumulate and interact with the tumor cells, which can be essential for achieving superior antitumoral effects [64]. On the other hand, the natural and synthetic polymers can also imprint a stimuli-responsive (e.g., pH, temperature, and enzymatic) behaviour on the metallic-based nanomaterials, which can be particularly advantageous for controlling drug delivery [33,[65][66][67][68]. In this regard, the heat generated by the nanomaterials (e.g., PTT and magnetic hyperthermia) can be also explored to induce phase changes in the polymers (e.g., Poly(N-isopropylacrylamide) (PNIPAM)) or increase their solubility, which will trigger the drug release [68,69].…”

In situ formation of alginic acid‐gold nanohybrids for application in cancer photothermal therapy

“…[16] To address these issues, gold nanoparticles are often combined with other materials, inorganic (e.g., silica) and/or organic (e.g., polymers), to improve nanoparticles' biocompatibility, stability, and tumor specificity. [16][17][18][19] The typical metal-polymer hybrid structures (metal core-polymer shells or polymeric core-metal shells) are prepared by establishing covalent bonds or electrostatic interactions between the surface of the gold nanoparticles and the polymer's functional groups. [20,21] Nevertheless, the synthesis methodologies explored in the literature for creating metalpolymer hybrid structures are usually time-consuming, complicated, and involve multiple steps, which compromise the scalability and consequently the translation of gold-based nanomaterials into clinical practice.…”