Nanographene-Au fine-tuning to intensify plasmonic-resonance of polymeric hybrid bionanosystem for synergistic phototherapy and nerve photobiomodulation

Cancer, the most serious disease with a leading cause of morbidity and mortality, is a disorder characterized by the unconstrained propagation of aberrant cells that can relocate, migrate, or penetrate other body organs through metastasis [1]. Breast cancer is on the top of cancer patients' charts with around 2.3 million cases, whereas colon cancer contributed 1.93 million cases and is the second most common reason for cancer-related deaths [1], [2], [3], [4]. Also, there are more than 13% chances of rectal and 5% chances of occurrence of colon cancer after breast cancer in women [5], [6], [7]. Moreover, there are unsatisfactory treatment outcomes with serious side effects of commonly used cancer therapies viz., surgery, radiotherapy, and chemotherapy [8], [9]. One major overlooked side effect is intraoperative peripheral nerve injury during colorectal surgery and breast surgery procedures; there are 3.8 million cases of long-term side effects including peripheral neuropathy in the United States alone in 2020 [10]. It has been reported that there are 13–15% risk of any nerve injury and the latest survey showed that 62.5% experienced chemotherapy-induced peripheral neuropathy after completion of chemotherapy [11]. Moreover, in the context of breast reconstruction, sensation loss is a great challenge, and hence, nerve tissue regeneration plays a very important role [12]. Therefore, there is a pressing need to develop highly functional biomaterial for more precise and prompt diagnostic approaches and efficient therapies for cancer treatment and to heal peripheral nerve damage [13], [14].

Nanotechnology-proclaimed photothermal therapy (PTT), in which conversion of light to heat induces cell death through hyperthermia, causes minimal damage to healthy tissues, and high impact on tumor ablation holds great promise for cancer treatment [15], [16], [17], [18]. The desired PTT effect can be achieved by structural modification of nanoparticles to have a high absorption cross-section in the NIR region (700–1400 nm) [19], [20], [21], [22]. Among numerous metal nanomaterials, gold (Au) nanomaterials possess excellent optical, photothermal, and physicochemical properties and were utilized for photothermal hyperthermia-based therapies [23], [24], [25], [26]. Gold nanospheres (AuNPs), while compared to gold nanostructures, are particularly attractive because of their easy methods of synthesis, uncomplicated surface functionalization, and simpler bio-conjugation [25], [27]. However, AuNPs lack maximum absorption peak in the NIR region as their plasmon resonance band lies in the 500–550 nm (visible region) and therefore require surface functionalization to be NIR active [28], [29], [30]. The appropriate technique to assist AuNPs for biomedical applications could be utilizing graphene as a protective and bifunctional layer in biological environments [31]. Graphene-based nanomaterials have strong NIR light-absorbing properties, large surface-to-volume ratio of 2630 m2/g, sturdy mechanical strength of ∼1100 GPa, exceptional electrical conductivity of 1738 siemens/m, superlative thermal conductivity of 5000 W/m/K, low toxicity, easy to functionalize, and higher penetration in cancer tumors [32], [33]. Yet, the size of graphene sheets is highly important and crucial for optimum efficiency [34].

Also, during prolonged laser irradiation, the graphene layer increases the thermal stability of gold nanoparticles [35], [36], [37]. Many literature reports related to gold-graphene nanohybrid are available though there is enough room for possibilities to enhance their efficacy with an appropriate strategy. Moreover, advanced-stage biomaterials are trying to minimize the concentration of inorganic nanomaterials by improving their biomedical efficiency [38], [39]. To address the issue, combining gold-graphene nanohybrid with biocompatible polymeric nanofibers could be an interesting approach [40], [41], [42]. In this regard, FDA-approved and easily available polycaprolactone (PCL) based nanofibers possibly will be a great option due to their non-toxic nature, porosity, good tensile strength, and overall extracellular matrix (ECM) like structure [43], [44], [45]. Polycaprolactone is synthesized by polymerization of caprolactone which is derived from various animal fats and oils in the form of fatty acid caproic acid. In addition, the aligned-oriented nanofibrous scaffolds can have higher cell proliferation with the migration of neural cells, cell outgrowth, and extracellular matrix accumulation inclined to stretch along the nanofiber alignment [46], [47], [48].

However, the incorporation of a minimum amount of gold-graphene nanohybrids in PCL is a challenging task, and synthesizing a biodegradable biomaterial for multiple photoactive bio-applications such as different cancer therapies and tissue regeneration is more challenging as well as inspiring. Therefore, to enhance the efficiency of graphene as well as the gold-graphene hybrid a new strategy has been used in the present study; graphene oxide micro sheets (800 nm) have been first chemically reduced and then fragmented into smaller sheets (180 nm) and then finally coated electrostatically with AuNPs. The resulting Gold-graphene hybrids (nRGO@AuNP) were dissolved in the polymer solution and electrospun to prepare PCL-based aligned nanofibrous scaffolds (nRGO@AuNP-PCL). The nRGO@AuNP-PCL nanofibrous scaffolds were then utilized for breast cancer (MCF-7) and colon cancer (CT-26) photothermal therapy and further, checked the efficacy of prepared nanofibrous scaffolds for the peripheral nerve regeneration.

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