Experimental and Theoretical Investigations in Stimuli Responsive Dendrimer-based Assemblies

Overview

Journal Nanoscale

Specialty Biotechnology

Date 2014 Sep 27

PMID 25260107

Citations 11

Authors

Mijanur Rahaman Molla

Poornima Rangadurai

Giovanni M Pavan

S Thayumanavan

Affiliations

Soon will be listed here.

Abstract

Stimuli-responsive macromolecular assemblies are of great interest in drug delivery applications, as it holds the promise to keep the drug molecules sequestered under one set of conditions and release them under another. The former set of conditions could represent circulation, while the latter could represent a disease location. Over the past two decades, sizeable contributions to this field have come from dendrimers, which along with their monodispersity, provide great scope for structural modifications at the molecular level. In this paper, we briefly discuss the various synthetic strategies that have been developed so far to obtain a range of functional dendrimers. We then discuss the design strategies utilized to introduce stimuli responsive elements within the dendritic architecture. The stimuli itself are broadly classified into two categories, viz. extrinsic and intrinsic. Extrinsic stimuli are externally induced such as temperature and light variations, while intrinsic stimuli involve physiological aberrations such as variations in pH, redox conditions, proteins and enzyme concentrations in pathological tissues. Furthermore, the unique support from molecular dynamics (MD) simulations has been highlighted. MD simulations have helped back many of the observations made from assembly formation properties to rationalized the mechanism of drug release and this has been illustrated with discussions on G4 PPI (Poly propylene imine) dendrimers and biaryl facially amphiphilic dendrimers. The synergy that exists between experimental and theoretical studies open new avenues for the use of dendrimers as versatile drug delivery systems.

Citing Articles

Rapid conjugation of nanoparticles, proteins and siRNAs to microbubbles by strain-promoted click chemistry for ultrasound imaging and drug delivery.

Liu X, Gong P, Song P, Xie F, Lee Miller 2nd A, Chen S Polym Chem. 2022; 10(6):705-717.

PMID: 36187167 PMC: 9523532. DOI: 10.1039/c8py01721b.

Programmed supramolecular nanoassemblies: enhanced serum stability and cell specific triggered release of anti-cancer drugs.

Mondal S, Saha M, Ghosh M, Santra S, Khan M, Das Saha K Nanoscale Adv. 2022; 1(4):1571-1580.

PMID: 36132617 PMC: 9418062. DOI: 10.1039/c9na00052f.

Surface Engineered Dendrimers: A Potential Nanocarrier for the Effective Management of Glioblastoma Multiforme.

Sahoo R, Gupta T, Batheja S, Goyal A, Gupta U Curr Drug Metab. 2022; 23(9):708-722.

PMID: 35713127 DOI: 10.2174/1389200223666220616125524.

Functionalization of Nanoparticulate Drug Delivery Systems and Its Influence in Cancer Therapy.

Seidu T, Kutoka P, Asante D, Farooq M, Alolga R, Bo W Pharmaceutics. 2022; 14(5).

PMID: 35631699 PMC: 9145684. DOI: 10.3390/pharmaceutics14051113.

Molecular bases for temperature sensitivity in supramolecular assemblies and their applications as thermoresponsive soft materials.

Liu H, Prachyathipsakul T, Koyasseril-Yehiya T, Le S, Thayumanavan S Mater Horiz. 2021; 9(1):164-193.

PMID: 34549764 PMC: 8757657. DOI: 10.1039/d1mh01091c.

References

Medina S, El-Sayed M . Dendrimers as carriers for delivery of chemotherapeutic agents. Chem Rev. 2009; 109(7):3141-57. DOI: 10.1021/cr900174j. View

Jiwpanich S, Ryu J, Bickerton S, Thayumanavan S . Noncovalent encapsulation stabilities in supramolecular nanoassemblies. J Am Chem Soc. 2010; 132(31):10683-5. PMC: 2923926. DOI: 10.1021/ja105059g. View

Yesilyurt V, Ramireddy R, Azagarsamy M, Thayumanavan S . Accessing lipophilic ligands in dendrimer-based amphiphilic supramolecular assemblies for protein-induced disassembly. Chemistry. 2011; 18(1):223-9. PMC: 3345162. DOI: 10.1002/chem.201102727. View

Tian W, Ma Y . Molecular dynamics simulations of a charged dendrimer in multivalent salt solution. J Phys Chem B. 2009; 113(40):13161-70. DOI: 10.1021/jp906449g. View

de Groot F, Albrecht C, Koekkoek R, Beusker P, Scheeren H . "Cascade-release dendrimers" liberate all end groups upon a single triggering event in the dendritic core. Angew Chem Int Ed Engl. 2003; 42(37):4490-4. DOI: 10.1002/anie.200351942. View

Kono K, Kojima C, Hayashi N, Nishisaka E, Kiura K, Watarai S . Preparation and cytotoxic activity of poly(ethylene glycol)-modified poly(amidoamine) dendrimers bearing adriamycin. Biomaterials. 2008; 29(11):1664-75. DOI: 10.1016/j.biomaterials.2007.12.017. View

Simanek E, Enciso A, Pavan G . Computational design principles for the discovery of bioactive dendrimers: [s]-triazines and other examples. Expert Opin Drug Discov. 2013; 8(9):1057-69. DOI: 10.1517/17460441.2013.813479. View

Betancourt J, Rivera J . Hexadecameric self-assembled dendrimers built from 2'-deoxyguanosine derivatives. Org Lett. 2008; 10(11):2287-90. PMC: 2654094. DOI: 10.1021/ol800701j. View

Rajasekhar Reddy R, Raghupathi K, Torres D, Thayumanavan S . Stimuli Sensitive Amphiphilic Dendrimers. New J Chem. 2013; 36(2):340-349. PMC: 3770314. DOI: 10.1039/C2NJ20879B. View

10.

Vaupel P, Kallinowski F, Okunieff P . Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989; 49(23):6449-65. View

11.

Jochum F, Theato P . Temperature- and light-responsive smart polymer materials. Chem Soc Rev. 2012; 42(17):7468-83. DOI: 10.1039/c2cs35191a. View

12.

Garzoni M, Cheval N, Fahmi A, Danani A, Pavan G . Ion-selective controlled assembly of dendrimer-based functional nanofibers and their ionic-competitive disassembly. J Am Chem Soc. 2012; 134(7):3349-57. DOI: 10.1021/ja206611s. View

13.

Shamis M, Lode H, Shabat D . Bioactivation of self-immolative dendritic prodrugs by catalytic antibody 38C2. J Am Chem Soc. 2004; 126(6):1726-31. DOI: 10.1021/ja039052p. View

14.

Szalai M, Kevwitch R, McGrath D . Geometric disassembly of dendrimers: dendritic amplification. J Am Chem Soc. 2003; 125(51):15688-9. DOI: 10.1021/ja0386694. View

15.

Navath R, Kurtoglu Y, Wang B, Kannan S, Romero R, Kannan R . Dendrimer-drug conjugates for tailored intracellular drug release based on glutathione levels. Bioconjug Chem. 2008; 19(12):2446-55. PMC: 2727757. DOI: 10.1021/bc800342d. View

16.

Aathimanikandan S, Savariar E, Thayumanavan S . Temperature-sensitive dendritic micelles. J Am Chem Soc. 2005; 127(42):14922-9. DOI: 10.1021/ja054542y. View

17.

Meers P . Enzyme-activated targeting of liposomes. Adv Drug Deliv Rev. 2001; 53(3):265-72. DOI: 10.1016/s0169-409x(01)00205-8. View

18.

Sirsi S, Borden M . State-of-the-art materials for ultrasound-triggered drug delivery. Adv Drug Deliv Rev. 2014; 72:3-14. PMC: 4041842. DOI: 10.1016/j.addr.2013.12.010. View

19.

Garzoni M, Okuro K, Ishii N, Aida T, Pavan G . Structure and shape effects of molecular glue on supramolecular tubulin assemblies. ACS Nano. 2013; 8(1):904-14. DOI: 10.1021/nn405653k. View

20.

Raghupathi K, Azagarsamy M, Thayumanavan S . Guest-release control in enzyme-sensitive, amphiphilic-dendrimer-based nanoparticles through photochemical crosslinking. Chemistry. 2011; 17(42):11752-60. PMC: 3343743. DOI: 10.1002/chem.201101066. View