Copper sulphide based heterogeneous nanoplatforms for multimodal therapy and imaging of cancer: Recent advances and toxicological perspectives

Highlights

• Detailed discussion on synthesis and morphology modulation of copper sulphide nanostructures.

• Copper sulphide based multimodal therapeutic strategies.

• Copper sulphide multimodal imaging probe in cancer.

• Copper sulphide based receptor targeted therapy of cancer.

• Toxicity aspects of Copper sulphide nanostructures.

Abstract

Inorganic nanostructures have emerged as potential nanoplatforms for cancer therapy and imaging. The clinical translation of mesoporous silica nanoparticles after iron nanoparticles have led to growing interest in these nanoplatforms. The present review presents copper sulphide based nanostructures as a versatile platform for multimodal therapy and imaging of cancer. This review gives a detailed description of various synthesis methods of copper sulphide nanostructures and also discusses the various factors which can help in modulating the morphology of copper sulphide based nanostructures. The article further sheds light on the unique thermal, electronic and optical properties of these nanostructures which holds potential for biomedical applications. The role of copper sulphide nanostructures in serving as therapeutic platforms for cancer therapy has been explained along with alternative therapeutic approaches apart from chemotherapy for cancer including photothermal therapy, photodynamic therapy, radiotherapy and gene therapy. The review also inculcates the potential of copper sulphide nanoplatforms for multimodal imaging ability including MRI, radio-imaging, fluorescence imaging and photoacoustic imaging. The theranostic nanoplatform based on copper sulphide nanostructures have also been overviewed. The role of copper sulphide nanostructures in receptor targeted therapy of cancer has also been discussed in brief for better understanding of its role in targeted cancer therapy. The article gives insight about the toxicological issue associated with cooper sulphide nanoparticles and also provides regarding the recent advancements in copper sulphide nanostructures including nano-heterostructures and metal organic frameworks for future biomedical application.

Introduction

In precision medicine, versatile nanoplatforms with greater diagnostic and therapeutic scope have drawn attention recently [1], [2], [3], [4]. In comparison to the other inorganic nanoparticles (NPs) researched for theranostic purposes, some of them like iron oxide, gold and silica are at the forefront [5], [6]. Furthermore, inorganic NPs draw more attention in pre-clinical and clinical phases of the drug design and growth due to their notable results. The versatility to the therapeutic and diagnostic design of inorganic nano-tools has proved them to be the feasible candidature for the potential applications. The Iron oxide NPs in the clinical trials against numerous kinds of cancer are identified as nano theranostic platforms [7], [8]. Also explored in clinical trials for the heat tumour ablation and cancer imaging are silica NPs and gold NPs (GNPs). Copper sulphide NPs (CuS NPs) are similarly powerful theranostic nanoplatforms with capable results [9], [10], [11]. This review describes the different CuS NPs explored in the field of cancer theranostics, as an evolving and adaptable nanoplatforms including their synthesis methods, morphological features and properties.

The CuS NPs as semi-conductors for their multifunctional characteristics have been widely studied [9]. Due to their varied diagnostic and therapeutic potential, they also appeared as adaptable and promising agents for the cancer theranostics [12], [13], [14]. This nanoparticle attracts maximum attention among multiple inorganic products due to biocompatibility, low price and low toxicity [12], [14], [15]. The absorption of CuS NPs by near-infrared (NIR) is obtained from d–d transformation of Cu²⁺ ions, showing NIR absorption in 700–1100 nm range. The absorption is not reliant on dielectric constant of adjacent medium and differentiates with design negligibly [15], [16], [17]. By contrast, the absorption of GNPs, which banks on surface plasmon resonance (SPR), decreases at a minimum power density of the 1 W/cm² after the laser irradiation for 60 min due to the melting effect [16]. It is possible to avoid the deleterious effects of NPs if they can be scraped effectively from the body without any accumulation in vivo. In a polycrystalline study, CuS NPs were disintegrated into small particles (SCuS NPs), which simplified the eradication method [13]. A contrast of the CuS NPs and the GNPs of comparable morphological design and particle size reveals that the non-biodegradable features of GNPs make it non-metabolizable in the character; nonetheless, due to their better biodegradability, CuS NPs can be effectively metabolized [18]. CuS NPs are withdrawn by hepatocytes through hepatobiliary excretion after Cu metabolism. Collective Cu removal from both renal excretion and hepatobiliary was estimated to be about 90% within one month after CuS NPs were injected. By contrast, at the same time course, i.e. one month, 3.98% Au was eradicated through the liver and kidney. After GNP injection, persistent toxicity was identified, while CuS NPs were quickly removed from the body due to their degradation and metabolism and are therefore ideal for clinical implementation amongst all inorganic nanomaterials.