Cancer is the second greatest cause of mortality worldwide and a serious health concern and is characterized by the uncontrolled growth and spread of aberrant cells [[1], [2], [3], [4]] [[1], [2], [3], [4]] [[1], [2], [3], [4]]. Multiple risk factors may contribute to the development of the disease, yet the origins of cancer are unknown [[5], [6], [7], [8], [9], [10]] [[5], [6], [7], [8], [9], [10]] [[5], [6], [7], [8], [9], [10]]. Proto-oncogenes that are responsible for encoding the protein that aids in tumor cell development and differentiation as well as tumor-suppressing genes that code for proteins that block the growth of developing cells, leading to apoptosis, are imbalanced or damaged in tumors leading cancer progression [[11], [12], [13], [14], [15], [16], [17]] [[11], [12], [13], [14], [15], [16], [17]] [[11], [12], [13], [14], [15], [16], [17]]. Chemotherapy, which uses tiny, cytotoxic chemotherapeutic agents to cause cell death in cancer tissues, is the most often used cancer treatment strategy besides surgery, radiation therapy, and immunotherapy. However major downsides of chemotherapy include drug toxicity, rapid degradation, low specificity, and restricted targeting which necessitates a drug delivery mechanism that may mitigate these drawbacks [[15], [16], [17], [18], [19], [20], [21], [22], [23]] [[15], [16], [17], [18], [19], [20], [21], [22], [23]] [[15], [16], [17], [18], [19], [20], [21], [22], [23]]. Current ongoing research has concentrated on improving existing techniques for killing cancerous cells in a more targeted manner while safeguarding healthy cells.

Targeted therapy aims to provide a carrier system that permits more focused, effective action for dosing methods, novel therapeutic targets (such the blood vessels, proteins, or genes that promote tumor growth), and tailored medicines [[24], [25], [26], [27], [28], [29]]. The development of nanomedicine as an offshoot of the swift advancement in nanotechnology offers enormous potential for the advancement in cancer treatment methods [6,23,30] [[6], [23], [30], [31], [32], [33], [34], [35]] [[6], [23], [30], [31], [32], [33], [34], [35]]. Innovative tailoring techniques and multifunctionality can be achieved using nanomedicine pharmaceuticals. Nanosystems with unique features that enable molecular recognition of the specific receptor or prompt delivery of the cargo at the illness site are being developed to improve the treatment efficacy of the medicine and reduce its negative impact on healthy tissues [3,[36], [37], [38], [39], [40], [41], [42], [43], [44]].

Discovered in 1970, the arginine-glycine-aspartate (RGD) tripeptide, also referred to as the RGD sequence, is a cell adhesion ligand that facilitates attachment among cells and extracellular matrix proteins[45,46]. This is accomplished by supporting excellent interactions between drug delivery systems consisting of nanoparticles (NPs) and various integrins. An amplification of the integrin αvβ3 on the angiogenic vasculature in tumors and unhealthy tissues has been demonstrated, making it a suitable candidate for targeting in anti-angiogenesis approaches. For use in medical applications, several different peptides comprising an RGD sequence have indeed been engineered as potential ligands for the αv integrin [47]. Along with linear RGD, the cyclic arginine-glycine-aspartic acid-phenylalanine-lysine peptide, abbreviated as cRGDfK, has been typically used because of its potential to preferentially attach to the αvβ3 adhesion molecules with great specificity [48]. Moreover, additional peptides containing RGD were also documented for their exceptional efficacy, including multimeric (RGD)4 [49,50], iRGD [51] and bicyclic RGD that shows equisite selectinvity for various types of integrins [52,53]. iRGD exhibits a greater binding affinity for αv integrins in contrast to linear as well as cyclic RGD peptides, falling within the mid-to low-nanomolar range [51,54,55]. The cyclization of iRGD occurs through the side groups of two terminal cysteines in the cyclo(-CRGDKGPDC-) sequence. iRGD is now regarded as the most potent RGD-based integrin binder in the field of cancer therapy for many types of cancer [56]. A highly efficient medication or gene delivery mechanism that selectively targets cancerous cells while protecting normal healthy cells is a necessity for cancer treatment. This improves the efficiency of treatment while safeguarding healthy cells from cytotoxicity. A specialized cyclic RGD version, known as cyclo[RGDfK(C-ε-6-aminocaproic acid)], was specifically created for attaching to nanocarriers, such as micelles of micellular polyplexes [57]. Remarkably, the cycloRGD-decorated micelles exhibited a tendency to gather in the perinuclear region of HeLa cells that are abundant in αv integrins [58,59]. This discovery holds significant implications for the advancement of targeted delivery methods. Furthermore, including antibodies as specific elements in the development of Antibody-Drug Conjugates (ADCs) is a well-established method to reduce the exposure of healthy cells to harmful substances, hence improving the efficacy of treatment. Peptide-Drug Conjugates (PDCs), which are a type of Small Molecule-Drug Conjugates (SMDCs), have emerged as a viable alternative to Antibody-Drug Conjugates (ADCs). PDCs employ diminutive peptides or peptidomimetics as targeting components. This strategy has become increasingly popular due to a multitude of advantages. First and foremost, PDCs demonstrate enhanced pharmacokinetic characteristics in comparison to larger protein therapies. This facilitates quick and consistent buildup at the location of the tumor and improves the ability of cells to pass through. In addition, PDCs exhibit a remarkable affinity for the specific protein they target [60]. Nanoparticles/PDC, by providing favorable pharmacokinetics, biocompatibility, and excellent tumor specificity, represent viable drug delivery alternatives to traditional pharmaceuticals. This review aims to describe distinct RGD-based nanoparticles as prospective drug delivery methods in particular forms of cancer by targeting integrins effectively. This article also provides a summary of the administration of numerous chemotherapeutic drugs via these systems, as well as their significance and prospects (Fig. 1).