advancement in the field of nano - biomedical technology has attracted scientists to explore the domains to conjugate potentially active biomolecules with nanoparticles which can bring forward some cost - effective drugs as future medicine . one such approach would be to conjugate therapeutically potent venom - toxins of animal origin with nanoparticles for their unique properties to enhance their therapeutic value . bridging nanoparticles with venom - toxins can act as better interface for drug delivery , targeted therapy , and better cellular level interaction thereby increasing the efficacy of the venom toxin bio - molecule having medicinal value . venoms are mixtures composed of a large number of bioactive molecules , such as protein toxins , enzymes , and polypeptides . toxins are chemically pure , active substances present in the venom that have specific actions on the biological systems . though venoms - toxins cause patho - physiological conditions but also may turn out to be effective healers of many diseases . as paracelsus , the 15th century philosopher , had rightly said   in all things there is poison ; there is nothing without poison . it only depends upon the doses , whether a poison is a poison or not  . we now understand that in many cases it is the dose that differentiates a poison from a remedy , which means that any chemical can be toxic if the dose is high , and this is also the basis of modern toxicology . paracelsus also said that a poison can counteract another and this is the foundation of chemotherapy , antibiotics and immune prevention . it is now well accepted that a poisonous substance could be used as a drug by proper administration , while a life - saving drug might become a poison with indiscriminate use . use of venoms for treatment of various diseases finds mention in many ancient medicinal texts . in modern day research , detailed studies on the patho - physiological manifestations due to venom and toxin administration , have led scientists to discover logical application of the venom - toxins for developing therapeutically potent agents . therefore , nano - conjugation of these potential venoms - toxins can provide new insights in developing new drugs and effective treatment . venom research is being carried out throughout the world for more than 100 years ; using snake venom either as medical research tools or directly as therapeutic / diagnostic agent ( pal et al , 2002 ; gomes et al , 2010 ) . more than seventy - five years ago , it was proposed that the physiologically active components of snake venom might have therapeutic potential ( calmette et al , 1933 ) . thereafter , many reports have established the anticancer potential of different species of elapidae , viperidae and crotalidae snake venoms ( tu et al , 1974 ; iwaguchi et al , 1985 ; debnath et al , 2007 ) . contortrostatin , a toxin derived from agkistrodon contortrix , is an important component showing antineoplastic activity ( zhou et al , 1999 ) , which blocks several critical steps in tumor metastasis including angiogenesis . recent studies by park and co - workers reported a toxin from the venom of vipera lebetina turanica that caused apoptosis of human neuroblastoma cells ( park et al , 2009 ) . drct - i from indian daboia russellii venom , nk - ct1 from indian naja kaouthia venom and nn-32 from naja naja venom showed antineoplastic potential against human leukemic cells in vitro and eac bearing mice in vivo ( gomes et al , 2007 ; debnath et al , 2010 ; das et al , 2011 ) . antiarthritic activity of naja kaouthia venom has also been reported ( gomes et al , 2010 ) . notexin purified from venom of notechis scutatus scutatus was cytolytic towards neuroblastoma cells sk - n - sh cells via upregulation of fas and fasl protein expression through p38 mapk / atf-2 and jnk / c - jun pathways ( chen et al , 2010 ) . an enzyme agkistrodon antithrombogenase ( aat ) ameliorated clinical symptoms of rheumatoid arthritis ( cai et al , 2002 ) . batroxobin , a drug derived from defibrase purified from bothrops moojeni , has therapeutic application in acute cerebral infarction , non - specific angina pectoris and sudden deafness . captopril , a drug developed from bothrops jararaca venom , is used to treat kidney disease in diabetes , high blood pressure and heart failure . recently a novel glycoprotein 1b - binding protein jerdonibitin has been reported from trimeresurus jerdonii venom , which showed potent platelet inhibiting activity ( chen et al , 2011 ) . gomes and colleagues purified a hexapeptide , hannahpep , from indian king cobra , which showed strong fibrinolytic and defibrinogenating activity ( gomes and de , 1999 ) . they also identified kc - mmtx a 282 d non - protein toxin from the indian king cobra venom , which can produce cns depression ( saha et al , 2006 ) . venoms and toxins from amphibian skin also hold promise as medicinal agents like immunomodulatory , cardiotonic , anti - microbial , wound healing , anticancer ( gomes et al , 2007 ) . one mentionable amphibian toxin is the nonopioid analgesic epibatidine isolated from the skin of the ecuadorian poison frog epipedobates tricolor by daly and co - workers shows highly potent nicotinic analgesic ( spande et al , 1992 ) and has longer duration of action than nicotine in analgesia and acts as a nicotine acetylcholine receptor agonist ( qian et al , 1993 ) . it has been suggested that epibatidine is a potent agonist of ganglionic nicotinic receptors and that the alkaloid elicits cardio - respiratory effects similar to those of nicotine ( fisher et al , 1994 ) . gomes and co - workers identified a non - protein crystal bm - anf1 and a protein bmp1 that possess anti - neoplastic potential ( gomes et al , 2007 ; bhattacharjee et al , 2011 ) venoms and purified toxins of invertebrates , particularly the arthropods ( including scorpion , centipede , bee and wasp ) have been reported to show therapeutic potential . chlorotoxin , a 36 amino acid peptide from scorpion leiurus quinquestriatus venom , is an effective inhibitor of glioma cell growth . since it is a high - affinity peptide ligand for cl- 144 channels and can block small conductance chloride channels , it can interact with chloride channels in membrane protein of glioma cells , thereby preventing trans - membrane chloride fluxes , but this interaction is absent for the neurons and normal glial cells ( debin et al , 1993 ; lyon et al , 2002 ; deshane et al , 2003 ) . a synthetic peptide of chlorotoxin named tm-601 has the ability to cross the blood brain barrier and is under clinical trial for treating glioma . stoppin , a 27 amino acid miniprotein derived from a toxin from venom of asian scorpion buthus martensi karsh can kill tumor cells in a p53 dependent manner ( li et al , 2008 ) . our group identified bengalin , a protein toxin from indian black scorpion heterometrus bengalensis , that had selective cytotoxic potential towards leukemic cells u937 and k562 ( das gupta et al , 2010 ) . kaliotoxin , a 4kd polypeptide neurotoxin derived from the scorpion androctonus mauretanicus mauretanicus can ameliorate multiple sclerosis and bone re - absorption due to periodontitis , in rat models ( beeton et al , 2001 and valverde et al , 2004 ) . mellitin , a 26 amino acid peptide from bee venom , can disrupt cell membrane and enhance phospholipase a2 activity and has various effects on living cells ( mollay et al , 1976 ; lad et al , 1979 ; cole et al , 1969 ; mufson et al , 1979 ) . it possesses potent antimicrobial property ( lubke et al , 1997 ) and inhibits the growth of the bacteria borrelia burgdorferi , kills candida albicans and suppresses mycoplasma hominis and chlamydia trachomatis infections . researchers worldwide have identified several other bioactive venom - toxins that were observed to possess certain medicinal properties . however , these molecules need to be properly harnessed and exploited to the fullest , so that they are ready to enter the stage of clinical trials . here comes the necessity for implementation of new technologies in the field of drug development and nanotechnology is one such application that shows promise in the field of nanomedicine . an important application of nanotechnology and nanomedicine is the development of new molecules with nano - scale dimensions for medical applications ( park et al , 2008 ) . nano - particles act as biological interface between bulk materials and atomic or molecular structures . this technology holds great promise in the field of medical science because of the unique physicochemical properties of nano - particles , such as ultra small size , large surface area - to - mass ratio , high reactivity , and effective interaction with cells , high stability , catalytic power and solubility . these nano - scale materials can be potential candidates of future medicine because of their effective routes of administration , better penetration capacity , lower therapeutic toxicity , efficient and specific target oriented drug delivery system and better interaction at cellular level . nano - particles have made an impact in the field of medicine by having applications such as biological labelling , drug and gene delivery , bio - detection of pathogens and proteins , dna and rna probes , enhancers in optical imaging processes , diagnostics , tissue engineering , separation of biological molecules and cells , combating diseases most importantly in tumour destruction and cancer treatment ( salata et al , 2010 ) . the unique capability of liposomal nano - particles to encapsulate efficiently with different ligands for targeted tissue oriented therapy , prolonged half life period in vivo , biocompatibility and specific formulation according to needed specificity makes them potent pharmaceutical carriers ( moghimi et al , 2003 ; torchilin et al , 2005 ) . carbon nano - tubes have been used as drug carriers and nano - devices ( yang et al , 2007 ) . nano - particles were found to improve contrast in mri , ultrasound and x - ray techniques thereby bringing new dimensions in bio - imaging techniques ( babes et al , 1999 ; liu et al , 2007 ; hainfield et al ; 2006 ) . nano - particles , such as liposomes , carbon nano - tubes and nano - gold , have been experimentally successful as drug delivery agents ( han et al , 2007 ) . carbon , fullerene , silicon dioxide , metal oxide , silver , magnesium oxide , zinc oxide , chitosan nanofiber , gold nano - particles have been experimentally proven to posses anti - bacterial properties ( mathews et al , 2010 ) . silver and gold nano - particles have diverse applications in the field of biology , medical diagnosis and therapy ( sadowski et al , 2008 ) . dendrimers has also emerged as drug delivery agents due to their unique structural architecture ( bhadra et al , 2003 ) . super - paramagnetic nano - particles ( spions ) have been used in magnetic detection and diagnostics ( johnson et al , 2010 ) . nano - particles conjugated with antibodies have been found to have potent interaction with biological systems ( sidorov et al , 2007 ) . it may be said that nanoparticles have made their remarkable impact and may play a potential role in almost all branches of medical science such as immunology , radiology , oncology , microbiology , orthopaedics , cardiology , ophthalmology and many more ( farokhzad et al , 2006 ) . nano - technology has radically changed the scenario of cancer therapy , by providing improved methods of detection , diagnosis , targeted drug delivery , tumour destruction ( kairemo et al , 2008 ) . research in the field of nano - technology focusing particularly on developments in nanomedicine has been a prime priority throughout the world to bring a new paradigm in the medical arena . in fact , interfacing living cells with engineered nanostructures is needed for biomedical applications for practical therapeutic approach . hence , nano - technology can be considered a boon to current research since its application can bring forward dramatic changes in medical science . nano - particles have unusual properties that can be used to improve the pharmacological and therapeutic properties of drugs . nanoencapsulation of these therapeutically potent molecules not only provides a media for better drug delivery but also enhance stability , bioavailability and targeted drug application . larger molecules may get eliminated from the body , but cells take up these nano - particles because of their size . hydrophylic nano - particles such as chitosan , nano - gold , nano - silver , magnetic and supermagnetic nano - particles , dendrimers , etc . , are being studied extensively in the role of drug delivery vehicles by conjugating them with several therapeutically potent venoms and toxins , particularly peptides , proteins and antigen . in addition to its potential in facilitating drug delivery , nano - technology has induced new perspective in therapeutic regime . the concept of smart nano - particle , nano - particle induced hyperthermia ( induced by laser in case of plasmonic nano - particle and radio frequency in case of magnetic nano - particle ) , use of nano rod in sub - cellular targeting ( e.g. , specific mitochondrial damaged by nano - rod ) are some of the examples of this new paradigm of therapy cum diagnostic .the fact that bare nano - particle can alter protein aggregation profile in vitro ( singha et al , 2010 ) as well as in vivo in cancer cell shows that the nanoparticles have both toxicological and therapeutic value which can not be questioned . similarly , the work by patra and coworkers shows the cytotoxicity of bare gold nano - particles and that of arginine conjugated gold nano - particle . it has also been shown that the efficacy of an anticancer drug can be improved by several folds by suitable nano - conjugation ( patra et al ; 2011 ; singha et al , 2011 ) . behfar and his co - workers have evaluated the antigen delivery potential of chitosan encapsulated naja naja oxiana venom ( mohammadpourdounighi et al , 2010 ) . chitosan is a hydrophilic biodegradable and non - toxic polysaccharide , which possesses excellent capacity for association with proteins and increased the permeability through cell membranes ( artursson et al , 1994 ; dodane et al , 1999 ) and could enhance the absorption of poorly absorbable drugs ( schipper et al , 1996 ) . by studying the chitosan encapsulation of the n. n. oxiana venom , they proposed the possible use of such nanoparticles as an alternative to the adjuvants that are in use currently . bombesin ( bbn ) peptides obtained from toad skin showed high affinity towards gastrin releasing peptide ( grp ) receptors that are over expressed in prostate , breast and small lung carcinoma in vivo . bbn were conjugated with gold nano - particle and also its radiolabelled substitute was developed ( chanda et al , 2010 ) . the constructs exhibited high binding affinity , being grp - receptor specific , showing high selectivity for grp - receptor rich prostate tumours in immune - deficient mice and also grp - receptor rich pancreatic acne in normal mice . the intra peritoneal mode of delivery was found to be effective as the bbn - gold conjugates showed reduced reticulo - endothelial system uptake by organs with concomitant increase in uptake at tumour targets . a bio - adhesive drug delivery system was developed with wheat germ agglutinin ( wga)-grafted lipid nano - particles for the oral delivery of bufalin ( a hydrophobic active component from skin secretion of chinese toad ( bufo bufo gargarizans ) . it was observed that wga enhanced the cellular uptake of nano - particles compared with wga - free lipid nanoparticles thereby indicating that wga grafted lipid nanoparticles could be a promising carrier to enhance cellular uptake with improved drug bioavailability through the oral route ( liu et al , 2010 ) . the disadvantages of mellitin are off - target toxicity , non - specificity and unfavourable pharmacokinetics . soman and co - workers developed a nano - conjugated mellitin where the toxin was incorporated into the outer lipid monolayer of a per fluorocarbon ( pfc ) nanoparticles ( soman et al , 2009 ) . this nano - carrier allows accumulation of mellitin in murine tumors in vivo and significant reduction in tumor growth without any apparent signs of toxicity . the nano - carriers could selectively deliver mellitin to multiple tumor targets through a hemidiffusion mechanism , where the surface membrane was not disrupted but it triggered apoptosis and also caused regression of precancerous dysplastic lesions in animals . by incorporating the mellitin into the nanovehicle , the wide - spectrum cytolytic potential could be restrained and made more specific . to enhance the medicinal activity of bee venom ( bv ) acupuncture , jeong and co - workers loaded bee venom into biodegradable poly(d , l - lactide - co - glycolide ) nanoparticles ( bv - plga - nps ) and observed that it could prolong the analgesic effect of plga - encapsulated bee venom on formalin induced pain in rats . from the experiments it was evident that plga - encapsulation was effective in alleviating the edema induced by allergens in bee venom indicating that plga - encapsulation provides a more prolonged effect of bv acupuncture treatment , while maintaining a comparable therapeutic effect ( jeong et al , 2009 ) . one of the toxins that have been exploited the most by nano - biotechnologists is chlorotoxin from the israeli scorpion leiurus quinquestriatus venom . zhang and his group used supermagnetic iron oxide as a nano - vector ( sun et al , 2008 ) conjugating it with a conventional therapeutic drug methotroxate and a targeting ligand chlorotoxin . the conjugated nano - particle resulted in successful attachment of both drug and the chlorotoxin demonstrating preferential accumulation and increased cytotoxicity towards glioma cells . moreover , prolonged retention of these nanoparticles was observed in the tumour cells in vivo . in another report zhang and co - workers developed supermagnetic iron oxide nanoparticle conjugated with an amine - functionalized polysilane and chlorotoxin ( veiseh et al , 2009 ) . it was observed that the nanoconjugation significantly enhanced cellular uptake of the toxin and inhibited cancer invasion by about 98% as compared to unbound toxin ( which was about 45% ) . chlorotoxin - enabled nanoparticles deactivated the membrane bound matrix metalloproteinase 2 and induced increased internalization of lipid rafts expressing mmp2 and ion channels on its surface , through receptor - mediated endocytosis . because of the combined imaging capacity as well as therapeutic effects of this nano - conjugated chlorotoxin , it might be a potential candidate for both non - invasive diagnosis as well as treatment for a variety of tumours . chlorotoxin was used in the development of a magneto fluorescent nano - probe conjugating iron oxide nanoparticle coated with biocompatible polyethyleneglycol - grafted chitosan copolymer with chlorotoxin and a near - ir flurophore ( veiseh et al , 2009 ) . this nano - probe could traverse the blood - brain - barrier , specifically target brain tumors and leave the blood brain barrier uncompromised . the mri detect ability combined with nirf illumination exhibited by the same nano - probe might allow its use in preoperative diagnostics , tumor resection , and postoperative assessment using magnetic resonance or optical imaging . sun and co - workers studied the peg - mediated synthesis process to produce highly stable iron oxide nanoparticle which showed tumor - specific accumulation through both magnetic resonance and optical imaging after conjugation with chlorotoxin and a near - infrared fluorescent dye [ cy5.5 ] ( sun et al , 2010 ) . in another study , nano - probes were prepared using polyethylenimine - coated hexagonal - phase nayf4 : yb , er / ce nano - particles and conjugating them with recombinant chlorotoxin to form good biocompatible probes which when intravenously injected into balb - c mice produced high contrast images when irradiated with near - infrared radiation , indicating highly specific tumor binding and direct tumor visualization . this high sensitivity and high specificity of the chlorotoxin nanoprobe may improve the diagnostic and therapeutic modalities in cancer patients in the near future ( yu et al , 2010 ) . recent researches have shown combination of walterinnesia aegyptia venom with silica nano - particles enhances the proliferative functioning of normal lymphocytes through cxcl12-mediated signaling through pi3k / akt , nfb and erk signalling ( gamal et al , 2012 ) . dounighi and his co - workers have demonstrated chitosan nanoparticles loaded with m. eupeus scorpion venom could be better sustained than with conventional venom loaded adjuvants and therefore , be an alternative option to traditional adjuvant systems ( dounighi et al , 2012 ) . pornpattananangkul et al reported recently about bacterial toxin enabled drug release from nanoparticle - stabilized liposomes providing new , safe , and effective approach for the treatment of bacterial infections ( pornpattananangkul et al , 2011 ) . there are recent reports by yu et al claiming rational design of a synthetic polymer nanoparticle that neutralizes a toxic peptide in vivo . the experiments established that the ( nps ) accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver therefore providing a platform to design plastic antidotes in future ( yu et al , 2011 ) . conjugation of venom - toxins with suitable nano - particles would not only provide insights to newer drugs but also better drug delivery systems which would have better therapeutic potential and biocompatibility . tables 1 provide a list of nano - conjugated venom - toxins ; which possess potential to be future therapeutic drugs / diagnostic probes table 2 therapeutic potential animal venom - toxins for future nano - conjugation . therapeutically active nanoparticle conjugated venom - toxins . ongoing dbt , govt of india , sponsored research project in the authors laboratory potential venom - toxins for future nanoparticles conjugation . nature remains the ultimate and major source of infinite biologically active compounds which can bring forward answers to many unresolved health problems , among which  venom - toxins  are pioneer candidates whose potentiality needs to be unveiled . the realization that venom - toxins are a store house of potential active compounds , which can efficiently interact with highly specific molecular targets are natural sources and not products from chemists test tube give them a better edge in drug development research compared to artificial chemical compounds which shows a new paradigm towards drug development clues . researchers throughout the world are now showing interests in developing nano conjugated toxins as life - saving drugs , with primary focus on maximizing bioavailability of the drug both at specific places in the body and over a period of time . it is interesting to note that whether nano - conjugation can provide the option of delivering the drug through different routes as per convenience . it has been observed that with development of nano - conjugated venoms - toxins , the therapeutic properties of the drugs improve significantly . also , site - directed targeting of the molecules may be achieved by nano - venoms - toxins . larger molecules may get eliminated from the body , but cells take up these nanoparticles because of their size . there is a possibility that due to the nano - conjugation , the nano - particle may act as an alternative to the traditional adjuvant systems , resulting in slow release of the drug to the target site and at the same time lowering the toxicity of the toxins to a large extent . worldwide research on nanomedicine implies that nano - conjugated venom - toxins hold good promise in the field of drug development and delivery but extensive research is necessary before the nano - based products can be considered for clinical trial . detailed study is warranted regarding the toxicity profile and bio - distribution of venom - toxin conjugated nanoparticles . the environmental consequences of utilizing the nano compounds should also be taken into account while considering drug development by nano conjugation . perhaps , the combination of venom - toxins and nanotechnology can bring forward a revolutionary renaissance in medical science which can set a benchmark in drug development research .
nano - medical approaches to develop drugs have attracted much attention in different arenas to design nanoparticle conjugates for better efficacy of the potential bio - molecules . 
 a group of promising candidates of this category would be venom - toxins of animal origin of potential medicinal value . 
 traditional systems of medicine as well as folklores mention the use of venom - toxins for the treatment of various diseases . 
 research has led to scientific validation of medicinal applications of venoms - toxins and many active constituents derived from venoms - toxins are already in clinical use or under clinical trial . 
 nanomedicine is an emerging field of medicine where nanotechnology is used to develop molecules of nano - scale dimension , so that these molecules can be taken up by the cells more easily and have better efficacy , as compared to large molecules that may tend to get eliminated . 
 this review will focus on some of the potential venoms and toxins along with nanoparticle conjugated venom - toxins of snakes , amphibians , scorpions and bees , etc . 
 , for possible therapeutic clues against emerging diseases .