Anti-cancer green bionanomaterials: present status and future prospects

ABSTRACT Cancer is one of the most common health problems responsible for outnumbered deaths worldwide. Nanomedicine plays an important role in developing alternative and more effective treatment strategies for cancer theranostics. However, the toxicity, high cost and nanoparticles (NPs) production complexity are some of the major issues that obstruct the use of existing nanomedicine. Recently, the green synthesis of biogenic NPs from plants and microbial sources has become an emerging field due to their safer, eco-friendly, simple, fast, energy efficient, low-cost and less toxic nature. Interestingly, NPs play a key role in diagnosis of tumor at the initial stage by allowing cellular visualization. Furthermore, prospective applications of green NPs include magnetically responsive drug delivery, anti-cancer activity, photo-thermal therapy and bio-imaging. The present review provides perspective on the use of anti-cancer green bionanomaterials with a focus on their present status and future prospects in the theranostics of cancer. GRAPHICAL ABSTRACT


Cancer: a global menace
According to the National Cancer Institute (NCI), United States (U.S), cancer contains over more than 100 types Institute (1). Besides, it is anticipated that the incidence of cancer by 2030 will reach around 21.7 million and there would be about 13 million deaths owing to aging and population growth. The latest report published in June 2016 by iMShealth (Institute for Healthcare Informatics) anticipates the global cancer treatment market to reach $150 Billion by 2020 Informatics (2).
Nevertheless, the tumor load in the future is likely to be considerably larger due to lifestyle adoption, leading to an increased risk of developing tumor, such as physical inactivity, cigarette smoking and unhealthy diet in the economically developing countries' society (3). Notably, cancer causes one in seven deaths globally, causing more deaths than malaria, tuberculosis and AIDS Society (3,4). Impressively, the largest proportion of cancer cases is in developing countries, accounting for around 57% of new cases and 65% of cancer-related deaths. In 2012, cancer caused premature deaths of about 4.3 million people and the number of premature cancer deaths are presumed to increase by 44% between 2012 and 2030 Organization (5). By 2025, it is estimated that in the industrialized world only 20-25% of the people will be aged over 65 years, and of those 50-60% who die of tumor will be aged over 75 years (6). On 1 January 2016, over 15.5 million of the population of the United States had a previous history of cancer disease. By 1 January, 2026, this number is estimated to increase to 20.3 million. Moreover, the high prevalent cancers in 2016 that affects women are uterine corpus (757,190), breast (3,560,570), and colon and rectum cancer (727,350). For men, prostate (3,306,760), melanoma (614,460), and colon and rectum (724,690) cancers are most common (7). Additionally, nearly 189,910 new cancer patients and about 69,410 cancer-related deaths were estimated among black people in 2016 in the United States, involving 95,920 cases among women and 93,990 cases in men. Although black people have higher death rates due to cancer than whites, the discrepancy has lessened for all types of cancer combined and for prostate and lung cancers (in males only).
Radiotherapy, chemotherapy and surgery are some of the cancer treatments which are used to improve a patient's life. Besides, one of the major problems in the cancer treatment process is the side-effects owing to conventional treatment strategies (8)(9)(10). Recent cancer research findings have enhanced understanding about carcinogenesis, the metastatic cascade and genetic factors that influence tumor growth and development. Overall, despite some progress in cancer control, incidence and death rates are increasing for cancer types. Recently, the applications of nanobiotechnology have revealed novel strategies for the treatment and diagnosis of cancer. Thereby, the current review article aims to highlight significant applications of biosynthesized green nanomaterials in cancer theranostics and the hurdles in their way to clinical trials.

Green bionanomaterials: an insight
Green bionanomaterials involving metals such as gold, silver, copper, titanium, zinc and iron prepared from different bio-sources, and have been reported for various biomedical applications (11). In addition, metal NPs are used in drug delivery, gene delivery, medicine, cell labeling, sensors, food packaging, wound dressings, etc. However, some applications of metal NPs are still under development such as magnetically responsive drug delivery, photo-thermal therapy and photoimaging ( Figure 1) (12)(13)(14). Although fabrication of NPs has attracted great interest for various physical and chemical processes, but there is an urgent need to explore alternative routes owing to some unsatisfying conditions of these methods such as the need for high temperature in the thermo-reductive process or intensive energy in the laser ablation process (15). Moreover, the fabrication of NPs by a chemical process may require toxic substrates, generates harmful wastes or requires large amounts of energy and even has low productivity (16). Hence, natural products and resources may ultimately prove to be more efficient and cost-effective. Remarkably, many plant extracts, algae and an extensive range of microorganisms containing bacteria, actinomycetes, fungi and yeast are reported to be proficient in synthesizing bionanomaterials, Priester et al.  (24). Interestingly, isolated chloroplasts were reported to be able to catalyze the biosynthesis of bionanomaterials. More interestingly, microalgae were designed for ecofriendly, scalable and permanent photobioreactors for sustainable and continuous fabrication of valuable bionanomaterials (15). Notably, the exact mechanism of biosynthesis of metal NPs is not well understood yet (25). However, it is believed that some enzymes play a role in bio-reducing metal ions to form metal NPs (26,27). Figure 2 shows the schematic mechanism of microbial-mediated synthesis of metal NPs (11). The negatively charged bacterial cell wall interacts electrostatically with metal ions having positive charge. In addition, the bioreduction process may be catalyzed by enzymes inside the cells or on the cell surface. Salunke et al. (28) suggested the role of Saccharomyces cerevisiae cell wall components, some proteins and alcoholic compounds in the synthesis and stabilization of MnO 2 NPs (28). The mechanism of extracellular microbial-mediated biofabrication of metal NPs is basically due to microbial nitrate reductase responsible for reduction of metal ions into metallic NPs (11). All the mentioned mechanisms lead to extracellular or intracellular fabrication of metal NPs. In case of phytosynthesis of metal NPs, it is believed that phytochemicals such as proteins, flavonoids, polyphenols, alkaloids, saponins, phenols, essential oils and polyols which are present in the plants extract play a main role in bio-reducing the metal ions, converting them to metal NPs and also capping of the synthesized NPs for stabilization (13,(29)(30)(31). The plant-mediated mechanism of biogenic silver NPs' (AgNPs') production is illustrated in Figure 3.
According to the literature, several studies reported nontoxicity and biocompatibility of some metal NPs in normal cell lines, but high toxicity in cancer cell lines. For instance, Anand et al. (95) reported notable antitumor activity of phyto-synthesized palladium NPs against A549, but no toxicity was found in human normal peripheral lymphocytes cells (95). Besides, Du et al. (96) reported plant-mediated synthesis and anticancer activity of AgNPs against Hela and A549 in the range of 1-5 µg/mL, but no significant cytotoxic effect was observed up to 10 µg/mL in normal HaCaT and also ≤ 2 µg/mL in Raw 264.7 (96). Similarly, Uma Suganya et al. (33) reported substantial in vitro anticancer activity of biosynthesized AuNPs (2-10 μg/mL) against MDA-MB-231, but no significant toxicity was found in normal HMEC in the range of 5-80 μg/mL, indicating considerable biocompatibility of NPs in normal cells (33). Also, Kummara et al. (97) showed very high cytotoxicity of green synthesized AgNPs against NCI-H460 at 240 ppm, but no cytotoxicity was found in normal HDFa (97). Furthermore, Singh et al. (98) reported not only remarkable cytotoxicity of phyto-fabricated AgNPs against A549 and HeLa above 5 μg/mL, but also no significant toxicity in normal RAW 264.7 (98). Further work showed antitumor effects of bio-fabricated AgNPs (0.02-50 µg/mL) against MCF-7; however, no cytotoxic effect was found in normal human blood mononuclear cells (99). In addition, Namvar et al. (58) reported biocompatibility of biological AuNPs in normal human blood mononuclear cells up to 100 µg/mL, but substantial cytotoxicity against cancer cell lines including CEM-ss, Jurkat, HL-60 and K562 (58). Likewise, Venkatesan et al. (76) showed biocompatibility of biosynthesized AuNPs in normal HaCaT in the range of 10-50 µg/mL (76). Furthermore, Yang et al. (87) reported no cytotoxicity of plantmediated synthesized AuNPs (10-160 μg/mL) in normal CV-1, WI-38 (87). Although these studies depicted biocompatibility of metal NPs, some studies are not in agreement. Specifically, Majeed et al. (100) reported fungus-mediated synthesis of AgNPs by using Penicillium decumbens (MTCC-2494) and assessed significant cytotoxic effects by MTT assay in the range of 20-120 μg/ mL against A-549 while 50% survival was demonstrated in the normal Vero cell line (100). In other study reported by Baharara et al. (101), as evidenced by MTT assay, biosynthesized AuNPs inhibit proliferation of HeLa cells (IC50:100 µg/mL) and normal bone marrow mesenchymal stem cells (IC50:300 µg/mL). However, cytotoxicity of AuNPs in bone marrow were lower than cancerous Hela cells (101). Likewise, Xia et al. (46) affirmed stronger cytotoxic effects of biogenic AgNPs (IC50: 27.75 µg/mL) against human cancerous hepatoma SMMC-7721 cells but showed lower cytotoxic against human normal liver (HL-7702) cells (IC50: 81.39 µg/mL) (46). Furthermore, Ma et al. (102) reported that the biosynthesized AgNPs, using a cell-free filtrate of the fungus strain Penicillium aculeatum Su1 as a reducing agent, presented higher biocompatibility toward human bronchial epithelial cells and high cytotoxicity in a dose-dependent manner with an IC50 of 48.73 μg/mL toward A549 cells. Additionally, Kasithevar (13) reported a simple and rapid synthesis of AgNPs using aqueous leaf extract of Alysicarpus monilifer mostly spherical in shape with a mean size of 15 ± 2 nm. Their study showed no cytotoxicity of AgNPs against Vero cell lines at the concentration of 200 µg/mL after 72 h of incubation. In contrast, Valli Nachiyar et al. (103) reported microbial-mediated synthesis of titanium dioxide (TiO 2 ) NPs. In their study, TiO 2 NPs were found to be more toxic against normal HaCaT (IC50: 55 μg/mL) than cancerous HEp2 cell lines (IC50:172 μg/mL) (103). Moreover, Lima et al. (104) reported genotoxic effects of microbial biosynthesized spherical AgNPs (Average size: 40.3 ± 3.5 nm) at concentrations of 5.0 and 10.0 μg/mL (104). In a study, natural anti-cancer flavone Chrysin (ChR), (5, 7-Dihydroxyflavone ChR), was used to synthesize AgNPs and AuNPs in a greener route without toxic additives. ChR strongly reduces Ag + and Au 3+ into their nano-forms with uniform size, shape and surface chemistry. In vitro anticancer results revealed that the prepared NPs exhibit enhanced cytotoxicity than ChR against treated two        The secondary metabolites have the polyhydroxy group which may be responsible for their role in the reduction of metal ions into NPs. In this study, the cytotoxicity of the synthesized AgNPs was investigated on the cancerous HL-60 cell line. The result represented that AgNPs synthesized using naringin as reducing agent had higher stability and better cytotoxic activity (107). Interestingly, a fish-intestine-associated bacterial strain was a potential source of exopolysaccharide (EPS) production reported with a significant ability to reduce iron-based materials and convert them to iron oxide nanoparticles (FeONPs). EPS was extracted from a spore-forming strain of Bacillus subtilis isolated from the gut microbiome of the freshwater fish Oreochromis mossambicus. In this study, the in vitro cytotoxicity effects of free EPS and EPS-stabilized FeONPs were probed in the human epidermoid carcinoma cell line A431. The IC50 values of EPS and EPS-stabilized FeONPs were found to be 350.18 and 62.946 mg/mL, respectively (108). In a study, AgNPs were biosynthesized by an aqueous leaf extract of Erythrina suberosa (Roxb.). Following that, the cytotoxicity of AgNPs was compared with plant extract and AgNO3 against the A-431 osteosarcoma cell line. The IC50 values were determined to be around 106.15, 74.02 and 136.73 μg/mL for leaf extract, AgNPs and AgNO3, respectively, indicating excellent anti-cancer activity of AgNPs among all (109). Notably, the exact mechanism of metal NPs' anti-cancer activity is not fully understood yet. However, it is believed that reactive oxygen species (ROS) generation, Sub-G1 arrest in cell, up-regulation of p53 protein and caspase-3 expression, inhibition of VEGF-induced activities are the major proposed anti-cancer mechanisms (21,110). Recent advances in the proposed mechanisms for anticancer activity shown by colloidal biogenic AgNPs are shown in Figure 4. Importantly, the ROS leads to activation of caspase-3 which is responsible for cell apoptosis by arresting the cell cycle at the G2/M phase (111). Besides, increased oxidative stress leads to oxidation of glutathione (GSH) to glutathione disulfide (GSSG) through the oxidation process. Notably, GSH is known as an antioxidant that prevents cells from ROS damages, consequently resulting in remarkably much MNPs' cytotoxicity and loss of GSH (24). Furthermore, AgNPs were shown to downregulate the activity of a recognized enzyme involved in DNA damage repair named DNA-dependent protein kinase (112). Coccini et al. (113) showed that the AgNP-induced oxidative stress genes involved Gpx1, SOD, FMO2 and GAPDH in different organs indicating AgNP-induced toxicity. The cytotoxicity of NPs may depend on parameters such as particle size, surface area and surface reactivity (115). Upon understanding the mechanism of metallic NPs' synthesis from plants and microbes, strategies can be designed for optimum synthesis of NPs of the desired shape and size. Eventually, based on heterogeneity of bio-sources, various factors such as temperature, synthesis conditions, reaction time, substrate concentrations and pH can have significant impacts on the rate of synthesis reaction.

Biocompatible nanomaterials for cancer diagnosis
Recent nano-medical developments helped the progress of NPs for diagnostic and therapeutic (theranostics) applications. Notably, NPs can play a vital role in cancer diagnosis at an early stage by allowing visualization of cancer cells. Cancer diagnostic instruments used routinely in preclinical research and clinical practice involve MRI, CT, ultrasound, optical imaging, positron emission tomography, photo-acoustic imaging and single-photon emission CT (SPECT). In this regard, these instruments differ based on their underlying physical principles, sensitivity and specificity to contrast agents, tissue contrast, spatial resolution, quantitativeness and tissue penetration (116). Remarkably, alpha fetal protein (AFP) is a cancer biomarker in clinical diagnosis associated with the disease progression and therapeutic responses of liver cancer. Xuan et al. (117) reported a plasmonic ELISA strategy by means of alkaline phosphatase-mediated growth of AgNPs for the colorimetric detection of serum AFP. This plasmonic ELISA provided high sensitivity displaying high performance in cancer diagnosis and therapeutic monitoring. This plasmonic assay is based on the in situ generation of AgNPs, leading to rapid color with various degrees of yellow, which can be easily performed on currently available instruments in clinical laboratories. Surprisingly, cancer detection has been widely investigated by applying metal NPs for marking tumor cells to find tumor-target fluorescence bio-imaging as an excellent fluorescent probe (118). Specifically, Ge et al., (118) reported biosynthesis of fluorescent Au/Ce nanoclusters (NCs) (1.2-2.2 nm) as highly sensitive bio-imaging agents. As demonstrated in Figure 5, the Au/Ce NCs show significant fluorescence in the HeLa cancer cells ( Figure 5A-C). Moreover, Figure 5D depicted the variations of fluorescence intensity between cancerous and normal cell types. Besides, the same results were obtained in HepG2 in the same situation. In contrast, the control group including L02 cells showed almost no intracellular fluorescence. Furthermore, according to the acceptable in vitro results, Au/Ce NCs were also investigated for in vivo bio-imaging in a tumor mice model of cervical carcinoma. As shown in Figure 6, fluorescence was observed around the tumor after 24 h of subcutaneous Au/Ce NCs injection (118). This is in agreement with the study of Wang et al., 2013, which demonstrated green synthesis of silver NCs employing glutathione and showed in vivo fluorescent tumor imaging through living animal tumors (119). Furthermore, Mukherjee et al. (120) reported green synthesis of monodispersed AgNPs (20-60 nm) by using Olax scandens leaf extract, with spherical shape and high stability for several days. In this study the fluorescence properties of biogenic AgNPs were observed through two cell lines (A549 & B16F10) employing a fluorescence microscopy. The untreated cells used as control and those treated with chemically fabricated AgNPs did not exhibit fluorescence, while those cancerous cells that were treated with biological synthesized AgNPs exhibited very strong fluorescence indicating the internalization of AgNPs by A549 & B16F10 cells (120). Overall, based on the aforementioned, the use of nanotechnology will be the best strategy for cancer diagnosis due to their self-fluorescence ability. One of the major drawbacks of current cancer treatment strategies is the lack of targeted drug delivery, resulting in systemic toxicity (8,121). Recently, magnetically targeted NPs have overcome this significant disadvantage of non-specificity as carriers for FDA-approved anti-cancer drugs. The basic principle is the loading of a particular anticancer drug on to a magnetic NP carrier like biocompatible super-paramagnetic iron oxide nanoparticles followed by injecting into the blood stream. Thereupon, with the application of external magnetic fields (highgradient), the particular drug delivery system (DDS) is targeted specifically at cancerous cells via changes in physiological conditions (osmolality, enzymatic activity and temperature). Indeed, by applying this strategy the associated side-effects along with the amount of the drug delivered are reduced, ultimately leading to reduced systemic toxicity (122,123). Seo et al. (124). have reported a novel study of biosynthesizing AuNPs via employing heavy metal binding proteins (HMBPs) of genetically engineered Escherichia coli acting as reducing, stabilizing and capping agent. The synthesized NPs were spherical in nature having a size of 5-20 nm in diameter. Furthermore, the group loaded doxorubicin (Dox) on the AuNPs@HMBPs DDS for treating the cancerous HeLa cells. The process of AuNPs@HMBPs' preparation along with Dox-loaded AuNPs@HMBPs' cytotoxic evaluation are illustrated in Figure 7

Hurdles for green nanomaterials as future cancer nanomedicine
A wide range of applications of metal nanoparticle therapeutics in the future is doubtless though there are still many challenges to be overcome and eventually routine clinical practice. If we talk about phytosynthesis, many amino acids, polysaccharides, flavonoids, alkaloids, vitamins, etc. exist in the metal NPs' medium method, which play a role in NPs' function, even if their surfaces are washed and purified since the residuals would stick to the NPs' surface. Likewise, in microbial synthesis, there are a number of microorganisms involving saprophytes and even pathogenic microbes such as E. coli introduced as a bio-source for preparation of metal NPs which would cause some hazards according to clinical studies. As an example, Aspergillus niger, Aspergillus flavus, Fusarium solani, etc. have been employed to biosynthesize metal NPs (26,(125)(126)(127)(128)(129). Importantly, another limitation is the protein corona effect, which occurs via adsorption of proteins on the colloidal NPs' surfaces when the nanoparticle enters the biological system (130). This adsorption actually compromises the ultimate dependability of NPs in the in vivo system (131). Overall, nanotechnology-based products are highly expensive probably due to difficulties in the manufacturing and preserving process; thereby its progress would cost a high amount of money. The key hurdles faced by researchers for entrance of biosynthesized NPs into the clinical phase have been graphically illustrated in Figure 8 (132)(133)(134).
By and large, many challenges and issues came in the way of scaling up nanoparticles/nanoconjugates'  production to industrial scale. NPs produced using routine top-down or bottom-up approaches in the lab vary greatly from those obtained from commercial producers. These approaches include sonication, emulsification, organic solvents evaporation and use, homogenization, centrifugation, elevated temperature, crosslinking and lyophilization (35). Practically, a slight change in the optimized conditions of NPs' synthesis can render the NPs biologically inactive, less stable and highly impure. Hence, a robust production process should be used at the labscale for NPs with an extraordinary reproducibility rate to be viable for large-scale commercial production.

Diffusion and penetration
In general, diffusive resistance of various tissues (intestine, vagina, nose mucosal membranes and lungs) poses a major barrier in nanomedicine delivery. Researchers have scientifically proved that the sedimentation and diffusion velocities of NPs highly affect their penetration and cellular uptake. Specifically, it is also reported that the cellular uptake and penetration are independent of surface coating, size, density, initial dose concentration and morphology of NPs (136). In addition, Cho et al. (137) reported that the shape dependency of AuNPs for their penetration through the cells could vary depending on their surface functional group. Wang et al.
(138) studied endocytosis of AuNPs with different sizes (45, 70 and 110 nm) in the human cancerous cell lines (CL1-0 and HeLa). This study revealed that the optimal size for the penetration into cells was around 45 nm. Interestingly, Chithrani et al. (139) evaluated the effect of spherical and rod-shaped AuNPs on cellular uptake in the HeLa cell line. This study depicted that spherical-shaped AuNPs had a higher cellular uptake in comparison to rod-shaped AuNPs because of variable biophysical properties such receptor diffusion kinetics. More interestingly, it was suggested that the surface coating of NPs impact on rate of uptake (140). For instance, Sur et al. (141) investigated cytotoxicity and cellular penetration of modified AgNPs with glucose, lactose, etc. in normal (L929) and cancerous (A549) cell lines. In this study, no differences were revealed in the cellular penetration of lactose-and glucose-modified AgNPs in L929, though there was a substantial growth in the cellular internalization of lactose-modified AgNPs into the A549, could be explained by the role of the chemical nature of the ligand in cellular uptake.

Toxicological and immunological aspect
Mukherjee and coworkers experimentally proved the nontoxic nature of these biogenic NPs in C57BL6/J female mice via various biochemical parameters along with a histopathology study of different organs. Even after successive injections of biogenic AuNPs (1 or 10 mg/kg/day) for seven days in healthy mice, no toxicity was observed (142). Moreover, it is interesting to note that in another study the same group reported that mice treated with chemically synthesized AuNPs showed broken alveolar walls with hyperplasic sinusoids as compared to the untreated or green synthesized AuNPs-treated mice (143). On the other hand, various chronic and acute toxicities of liver and nephrons were reported to be associated with zinc, platinum and cerium oxide NPs (144 -146). Hence, it is very crucial to screen the potential nanoparticles/nanomaterials for various toxicity studies including their pharmacokinetics, pharmacodynamics and responses to immune system before moving on to clinical trials (147-149 ).

Biodegradability, metabolic kinetics and clearance
Biodegradability is very vital aspect to be considered before exploiting AuNPs in vivo. Polymeric NPs are naturally biodegradable and are cleared form the body. However, in case of metallic NPs biodegradability is slow and poses serious challenges in terms of toxicity (50,147,151). Although detailed knowledge regarding the mechanism of metallic NPs' biodegradability and clearance is still unclear, few recent studies validate the gradual excretion of metal NPs in feces and urine even up to 14 days (147,152). Furthermore, the studies shed light on the positively charged AuNPs, which may encounter a negative charge repulsion from the glomerular basement membrane in nephrons and pass out via urine. In another study reported by Rengan and coworkers, liposomal AuNPs were demonstrated for their biodegradability and as a potential DDS for cancer therapy. Moreover, metabolic degradation of the delivery system was noticed in liver and hepatocytes followed by its easy excretion via the renal route (147). All the studies discussed in detail that in vivo biodistribution, metabolic kinetics, clearance and ultimate dependability of NPs are determined by their shape, size and morphology.

Conclusions and future prospects
Green nanomaterials are currently in a highly investigative phase for the treatment and diagnosis of cancer but the ultimate dependability is yet to be decided in clinical trials. A number of new possibilities have come into account in relation to the use of green nanomaterials, owing to their biocompatibility and effectiveness. Moreover, many types of cancers that do not have cures today may be cured by these green nanomaterials in the future.
Additionally, thorough understanding of key physiological barriers in vivo is the key to effectively deliver NPs into the tumor. Furthermore, the knowledge regarding the safety of nanomaterials is not sufficient and comprehensive acute and chronic toxicity in clinical studies should be observed to identify the hazards associated with the use of NPs. Considering the above discussion, it is expected that green nanomaterials could emerge as future cancer therapeutics and diagnostics agents in the near future.

Disclosure statement
No potential conflict of interest was reported by the authors.

Notes on contributors
Mr. Hamed Barabadi graduated as a Doctor of Pharmacy from Mazandaran University of Medical Sciences, Sari, Iran, 2014. He is currently working on his Ph.D. in Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. His main research interests are in nanobiotechnology with an emphasis on nanomedicine, nanobiomaterials and bioprocessing.
Mr. Muhammad Ovais is pursuing a Ph.D. degree in Nanomedicine from CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People's Republic of China. He has completed his MPhil-Biotechnology degree in 2017 from Quaid-i-Azam University, Pakistan and earned his BS-Biotechnology degree in 2015 with distinction from the University of Peshawar, Pakistan. His research interest lies in the development novel nano-delivery systems for cancer theranostics. He owns to his credit 19 original research and review articles in prestigious journals with a cumulative impact factor of above 50.