4. Challenges for the use of VLPs in nanomedicine

Bionanotechnology, as an emerging technological field, has opened a vast number of potential applications, in which biomedical applications are included. VLPs carrying different cargos could be effectively functionalized with different ligands to be recognized and cell-internalized for tissues containing the specific receptor. In spite of several advantages showed by the VLPs in the biomedical field, still there are some challenges to be solved to be practically used. These challenges are mainly related to the immunogenic response. Different strategies could be implemented to avoid the immune system recognition that includes the covering of the VLPs with a polymer such as polyethylene glycol or the genetic engineering of the viral coat proteins to mutate the epitopes more immunogenic [13]. The recent advancements in the bioinspired "active" stealth covers combining the property to reduce or eliminate the immunogenic response, and the active targeting, could be beneficial for treating diseased tissue via a biomimicry approach with lower side effects. The toxicity of VLPs should be also evaluated with emphasis on the fate of these nanoparticles in the organism and their possible side effects [38].

Another problem to be solved is the production of VLPs at large scale. Some VLPs can be easily produced at large scale, while others are hard to be expressed and purified. Research efforts are still necessary to have efficient systems of heterologous expression of coat proteins of VLPs [39].

We can conclude so far that the use of VLPs for biomedical and therapeutic purposes is still in its infancy but shows enormous potential, and thus research efforts are still needed. However, it is clear that the VLPs are excellent systems for several applications in the biomedical field including drug, enzyme and gene delivery, medical imaging, and biosensors. These virus-derived nanoparticles are promising candidates for the treatment and diagnosis of diseases.

increased tamoxifen cell sensitivity of both human cervix and breast tumor cells,

Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer.

Bionanoreactor of cytochrome P450 encapsulated in virus-like particle for the activation of prodrug tamoxifen

The multivalency and versatility of virus-derived nanovehicles were also used for targeted enzyme delivery in conjunction with the synergistic effect of

reducing the dose needed to kill these cells by 50% [35].

Figure 6.

Figure 7.

8

to the active drug for breast cancer treatment.

Technology, Science and Culture - A Global Vision, Volume II

Technology, Science and Culture - A Global Vision, Volume II

References

2004;304:1732-1734

2010;9:1149-1176

[1] Service, R. Nanotoxicology. Nanotechnology grows up. Science.

Viral Structures in Nanomedicine

Topics in Microbiology and Immunology. 2009;327:v-vi

[2] Manchester M, Steinmetz N. Viruses and nanotechnology. Preface. Current

DOI: http://dx.doi.org/10.5772/intechopen.90099

[11] Kreppel F, Kochanek S. Modification of adenovirus gene transfer vectors with synthetic polymers: A scientific review and technical guide. Molecular Therapy.

[12] Lee A, Wang Q. Adaptations of nanoscale viruses and other protein cages for medical applications. Nanomedicine NBM. 2006;2:137-149

[13] Abbing A, Blaschke U, Grein S, et al. Efficient intracellular delivery of a protein and a low molecular weight

polyomavirus-like particles. The Journal of Biological Chemistry. 2004;279:

[14] Zhao Q, Chen W, Chen Y, Zhang L, Zhang Z. Self-assembled virus-like particles from rotavirus structural protein VP6 for targeted drug delivery. Bioconjugate Chemistry. 2011;16:

[15] Ren Y, Wong S, Lim L. Folic acidconjugated protein cages of a plant virus: a novel delivery platform for doxorubicin. Bioconjugate Chemistry.

[16] Bar H, Yacoby I, Benhar I. Killing cancer cells by targeted drug-carrying

[17] Steinmetz N. Viral nanoparticles as

[18] Suci P, Gillitzer VZE, Douglas T, Young M. Targeting and photodynamic killing of a microbial pathogen using

functionalized with a photosensitizer. Langmuir. 2007;23:12280-12286

[19] Inoue T, Kawano M, Takahashi R, et al. Engineering of SV40-based

phage nanomedicines. BMC Biotechnology. 2008;8:37-40

platforms for next-generation therapeutics and imaging devices. Nanomedicine NBM. 2010;6:634-641

protein cage architectures

substance via recombinant

2008;16:16-29

27410-27421

346-352

2007;18:836-843

[3] Roldao A, Mellado M, Castilho L, Alves P. Virus-like particles in vaccine development. Expert Review of Vaccines. Expert Review of Vaccines.

[4] Lee A, Niu Z, Wang Q. Viruses and

virus-like protein assemblies-Chemically programmable nanoscale building blocks. Nano Research. Nano

[5] Strable E, Finn M. Chemical modification of viruses and virus-like

Microbiology and Immunology. 2009;

[6] Khalil A, Ferrer J, Brau R, et al. Single M13 bacteriophage tethering and stretching. Proceedings of the National Academy of Sciences of the United States of America. 2007;104:4892-4897

[8] Verma I, Weitzman M. Gene therapy: twenty-first century medicine. Annual Review of Biochemistry. Annual Review of Biochemistry. 2005;74:711-738

[10] Volpers C, Kochanek S. Adenoviral vectors for gene transfer and therapy. The Journal of Gene Medicine. 2004;6:

[7] Douglas T, Young M. Viruses: making friends with old foes. Science.

[9] Campos S, Barry M. Current advances and future challenges in Adenoviral vector biology and targeting. Current Gene Therapy. 2007;7:189-204

2006;312:873-875

S164-S171

11

Research. 2009;2:349-364

particles. Current Topics in

327:1-18
