Nanotechnology is shown to bridge the barrier of biological and physical sciences by applying nanostructures and nanophases at various fields of science [11]; specially in nanomedicine and nano based drug delivery systems, where such particles are of major interest [12, 13]. Nanomaterials can be well-defined as a material with sizes ranged between 1 and 100 nm, which influences the frontiers of nanomedicine starting from biosensors, microfluidics, drug delivery, and microarray tests to tissue engineering [14,15,16]. Nanotechnology employs curative agents at the nanoscale level to develop nanomedicines. The field of biomedicine comprising nanobiotechnology, drug delivery, biosensors, and tissue engineering has been powered by nanoparticles [17]. As nanoparticles comprise materials designed at the atomic or molecular level, they are usually small sized nanospheres [18]. Hence, they can move more freely in the human body as compared to bigger materials. Nanoscale sized particles exhibit unique structural, chemical, mechanical, magnetic, electrical, and biological properties. Nanomedicines have become well appreciated in recent times due to the fact that nanostructures could be utilized as delivery agents by encapsulating drugs or attaching therapeutic drugs and deliver them to target tissues more precisely with a controlled release [10, 19]. Nanomedicine, is an emerging field implementing the use of knowledge and techniques of nanoscience in medical biology and disease prevention and remediation. It implicates the utilization of nanodimensional materials including nanorobots, nanosensors for diagnosis, delivery, and sensory purposes, and actuate materials in live cells (Fig. 1). For example, a nanoparticle-based method has been developed which combined both the treatment and imaging modalities of cancer diagnosis [20]. The very first generation of nanoparticle-based therapy included lipid systems like liposomes and micelles, which are now FDA-approved [21]. These liposomes and micelles can contain inorganic nanoparticles like gold or magnetic nanoparticles [22]. These properties let to an increase in the use of inorganic nanoparticles with an emphasis on drug delivery, imaging and therapeutics functions. In addition, nanostructures reportedly aid in preventing drugs from being tarnished in the gastrointestinal region and help the delivery of sparingly water-soluble drugs to their target location. Nanodrugs show higher oral bioavailability because they exhibit typical uptake mechanisms of absorptive endocytosis.
Metallic, organic, inorganic and polymeric nanostructures, including dendrimers, micelles, and liposomes are frequently considered in designing the target-specific drug delivery systems. In particular, those drugs having poor solubility with less absorption ability are tagged with these nanoparticles [17, 29]. However, the efficacy of these nanostructures as drug delivery vehicles varies depending on the size, shape, and other inherent biophysical/chemical characteristics. For instance, polymeric nanomaterials with diameters ranging from 10 to 1000 nm, exhibit characteristics ideal for an efficient delivery vehicle [7]. Because of their high biocompatibility and biodegradability properties, various synthetic polymers such as polyvinyl alcohol, poly-l-lactic acid, polyethylene glycol, and poly(lactic-co-glycolic acid), and natural polymers, such as alginate and chitosan, are extensively used in the nanofabrication of nanoparticles [8, 30,31,32]. Polymeric nanoparticles can be categorized into nanospheres and nanocapsules both of which are excellent drug delivery systems. Likewise, compact lipid nanostructures and phospholipids including liposomes and micelles are very useful in targeted drug delivery.
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The use of ideal nano-drug delivery system is decided primarily based on the biophysical and biochemical properties of the targeted drugs being selected for the treatment [8]. However, problems such as toxicity exhibited by nanoparticles cannot be ignored when considering the use of nanomedicine. More recently, nanoparticles have mostly been used in combination with natural products to lower the toxicity issues. The green chemistry route of designing nanoparticles loaded with drugs is widely encouraged as it minimises the hazardous constituents in the biosynthetic process. Thus, using green nanoparticles for drug delivery can lessen the side-effects of the medications [19]. Moreover, adjustments in nanostructures size, shape, hydrophobicity, and surface changes can further enhance the bioactivity of these nanomaterials.
Yang et al. [49] prepared highly effective nanoparticles for revealing colorectal cancer (CC) cells via a light-mediated mechanism; these cells are visible owing to the physical conjugation of alginate with folic acid-modified chitosan leading to the formation of nanoparticles with enhanced 5-aminolevulinic (5-ALA) release in the cell lysosome. The results displayed that the engineered nanoparticles were voluntarily endocytosed by the CC cells by the folate receptor-based endocytosis process. Subsequently, the charged 5-ALA was dispersed into the lysosome which was triggered by less desirability strength between the 5-ALA and chitosan through deprotonated alginate that gave rise to the gathering of protoporphyrin IX (PpIX) for photodynamic detection within the cells. As per this research, chitosan-based nanoparticles in combination with alginate and folic acid are tremendous vectors for the definite delivery of 5-ALA to the CC cells to enable endoscopic fluorescent detection. Cathepsin B (CB) is strongly associated with the metastatic process and is available in surplus in the pericellular areas where this process occurs; thus, CB is important for the detection of metastasis. Ryu et al. [50] designed a CB-sensitive nanoprobe (CB-CNP) comprising a self-satisfied CB-CNP with a fluorogenic peptide attached to the tumor-targeting glycol chitosan nanoparticles (CNPs) on its surface. The designed nanoprobe is a sphere with a diameter of 280 nm, with spherical structure and its fluorescence capacity was completely extinguished under the biological condition. The evaluation of the usability of CB-sensitive nanoprobe in three rat metastatic models demonstrated the potential of these nonoprobes in discriminating metastatic cells from healthy ones through non-invasive imaging. Hyaluronic acid (HA) is another biopolymeric material. This is a biocompatible, negatively charged glycosaminoglycan, and is one of the main constituents of the extracellular matrix [51, 52]. HA can bind to the CD44 receptor, which is mostly over articulated in various cancerous cells, through the receptor-linker interaction. Thus, HA-modified nanoparticles are intriguing for their use in the detection and cure of cancer [53,54,55]. Wang et al. [56], coated the surface of iron oxide nanoparticles (IONP) with dopamine-modified HA. These nanoparticles have a hydrophilic exterior and a hydrophobic interior where the chemotherapeutic homocamptothecin is encapsulated [56]. The biopotential of this process was investigated in both laboratory and in the live cells. Increased uptake of nanoparticles by tumor cells was observed by MRI when an external magnetic field was employed [56]. After the intravenous administration of the nano-vehicle in 3 mg/kg (relative to the free drug) rats, a large tumor ablation was observed and after treatment, the tumors almost disappeared [56].
In this context, drug designing has been a promising feature that characterizes the discovery of novel lead drugs based on the knowledge of a biological target. The advancements in computer sciences, and the progression of experimental procedures for the categorization and purification of proteins, peptides, and biological targets are essential for the growth and development of this sector [66, 67]. In addition, several studies and reviews have been found in this area; they focus on the rational design of different molecules and show the importance of studying different mechanisms of drug release [68]. Moreover, natural products can provide feasible and interesting solutions to address the drug design challenges, and can serve as an inspiration for drug discovery with desired physicochemical properties [3, 69, 70].
Studies on their drug delivery-related activity have not been able to clear out whether the particulate or ionized form is actually related to their toxicity, and even though two mechanisms have been proposed, namely paracellular transport and transcytosis, there is not enough information about their in vivo transport and uptake mechanism [158]. Drugs can be conjugated to gold nanoparticles (AuNPs) surfaces via ionic or covalent bonding and physical absorption and they can deliver them and control their release through biological stimuli or light activation [159]. Silver nanoparticles exhibited antimicrobial activity, but as for drug delivery, very few studies have been carried out, for example, Prusty and Swain [160] synthesized an inter-linked and spongy polyacrylamide/dextran nano-hydrogels hybrid system with covalently attached silver nanoparticles for the release of ornidazole which turned out to have an in vitro release of 98.5% [160]. Similarly in another study, the iron oxide nanoparticles were synthesized using laser pyrolysis method and were covered with Violamycine B1, and antracyclinic antibiotics and tested against the MCF-7 cells for its cytotoxicity and the anti-proliferation properties along with its comparison with the commercially available iron oxide nanoparticles [161].
The lack of standard protocols for nanomedicines characterization at physico-chemical and physiological/biological levels has often limited the efforts of many researchers to determine the toxic potential of nano-drugs in the early stages of testing, and that resulted in the failures in late-phase clinical trials. To simplify and/or shorten the approval process for nano based medicines/drugs, drug delivery system etc., a closer cooperation among regulatory agencies is warranted [204, 251]. 2ff7e9595c