Future perspectives of Nanomedicine for HIV therapies

1. Search for strategies in the prevention of HIV, HSV-2 and other sexually transmitted viruses: intravaginal and rectal microbicides

2. Search for strategies to modulate/activate dendritic cells and/or macrophages to potentiate innate immune responses: Vaccine delivery

3. Role of innate immunity in the prevention and control of HIV infections

4. Human immunological and microbiological responses in small animal models and in human cervical biopsies

The Immuno-Biological Molecular laboratory works mainly upon the development of microbicides and vaccines against various infection diseases such as HIV, HSV…Nanoparticles biomedical applications aim at the study of nanoparticles (NP) focused specifically on the prophylactic development of vagina microbicide which will help women to stop having HIV and any other virus transmission.

Thanks to national and international projects, we have been carrying on in vitro, ex vivo and in vivo studies in various animal models to prove the efficacy of different NP against sexual transmission viruses with the aim of taking NP to clinical trials. We have been working on the role of specific NP for rectal uses. Our study includes experiments focused on men who have relations with men. We work upon various cellular lines to demonstrate the mechanism of NP to know at what viral cycle they perform, upon toxicological studies and the role of NP in cellular receptors as well as in the innate immune system. We work on different mice models including humanized mice and female rabbits. In addition, we have just started to work with vaginal tissue from healthy women.

Our target is to take microbicides, which stop sexually transmitted HIV infection, to clinical trials. Objectives of our studies are:

1. to prepare different cell lines to show that the selected NP have anti-HIV and/or anti-HSV effect in the first steps of viral replication, blocking the gp120/CD4/CCR5 interaction or…

2. to demonstrate that the selected NP are stable in various pH and in the presence of seminal fluid and that they keep their antiviral performance, and do not produce any resistance against viruses

3. to analyze the effect of NP on vaginal microbiome

4. to carry out histological studies on vagina mice and rabbits to show that NPs of various concentration and in different times do not cause irritation, inflammation, lesions or harm to the mucous

5. to show that NP inhibits the HIV infection more than 80% in vagina of humanized mice

6. Our group also work upon other research lines such as therapeutic and preventive vaccines using NP in the delivery of peptides, miRNAs or siRNAs in dendritic cells and macrophages

Mª Angeles Muñoz-Fernández               Alba Martín Moreno 
Jose Luis Jiménez                                   Ignacio Rodriguez Izquierdo
Rafael Ceña Diez                                    Ignacio Rodríguez Relaño                                        
Mª Jesús Serramia-Lobera

1.- ​Efecto de nuevas generaciones de dendrímeros con prevención dual frente al VIH/VHS-2: caracterización y prueba de concepto. PI16/01863 Amount: 272.552 € Funding source: Fondo Investigación Sanitaria (FIS). Instituto Salud Carlos III (ISCIII). Period: 2017-2019. Role of PL: PI.

2.-Red Investigación en SIDA (RED RIS) RD16/0025/0019 & RD 12/0017/0037. Funding source: FIS, ISCIII. Amount: 913.627 € for the last period. Period: 2012-2015 & 2016-2020. Role of PI: researcher of WPs, & Management Scientific Committee and Director of HIV BioBank.

3.-Early treated Perinatally HIV Infected individuals: Improving Children´s Actual Life (EPPICAL). Funding source: EPIICAL PENTA Foundation Project-ViiV & European Commission. Amount: 217.000 € Period: 2016-2020. Role of PI: Spain PL

4.-Desarrollo y mecanismo de acción de dendrímeros como microbicidas para frenar la infección por el VIH por transmisión sexual (vaginal y anal): prueba de concepto. PI13/02016. Amount: 261.057 €. Funding source: FIS. ISCIII. Period: 2014-2016. Role of PI: Coordinator.

5.-Plataforma Red Nacional de BioBancos PT17/0015/0042 & PT13/0010/0028. Funding source: FIS. ISCIII. Amount: 255.750 € for the last period. Period: 2013-2017 & 2018-2020. Role of PI: Scientific Director of HGM BioBank & Management Committee member.

1.-Chonco L, Pion M, Vacas E, Rasines B, Maly M, Serramía MJ, Lopez- Fernández L, de la Mata J, Alvarez S, Gomez R, Muñoz-Fernandez MA. Carbosilane dendrimer nanotechnology outlines of the broad HIV blocker profile. J Control Release, 2012, 161(3):949-958. IF:7.633 (1st Decilee). We showed a novel water-soluble dendrimer 2G-S16 as a propitious molecule against HIV-infection. We provided promising outcomes to encourage 2G-S16 as a hopeful microbicide.

2.-Briz V, Sepúlveda-Crespo D, Diniz AR, Borrego P, Rodes B, de la Mata FJ, Gómez R, Taveira N, Muñoz-Fernández MÁ Development of water-soluble polyanionic carbosilane dendrimers as novel and highly potent topical anti-HIV-2 microbicides. Nanoscale. 2015 Sep 21; 7(35):14669-83. IF:7,760 (1st Decilee). G2-S16 dendrimer deserves further studies as potential candidate microbicides to prevent vaginal/rectal HIV-1/HIV-2 transmission in humans.

3.-Sepúlveda-Crespo D, Serramía MJ, Tager AM, Vrbanac V, Gómez R, De La Mata FJ, Jiménez JL, Muñoz-Fernández MÁ. Prevention vaginally of HIV-1 transmission in humanized BLT mice and mode of antiviral action of polyanionic carbosilane dendrimer G2-S16. Nanomedicine. 2015 May 8. pii: S1549-9634(15)00107-0. IF:4,889. (1st Quartile). Vaginal administration of 3% G2-S16 prevents HIV-1 transmission in humanized (h)-BLT mice in 84% with no presence of HIV RNA and vaginal lesions. 

4.-Sepúlveda-Crespo D, Ceña-Díez R, Jiménez JL, Muñoz-Fernández MA. Mechanistic Studies of Viral Entry: An Overview of Dendrimer Based Microbicides As Entry Inhibitors Against Both HIV and HSV-2 Overlapped Infections. Med Res Rev. 2017 Jan; 37(1):149-179. IF: 8,763 (1st Decilee). It is an overview of dendrimers against HIV/HSV-2 as topical microbicides targeting the viral entry process. 

5.-Ceña-Diez R, García-Broncano P, Javier de la Mata F, Gómez R, Resino S, Muñoz-Fernández M. G2-S16 dendrimer as a candidate for a microbicide to prevent HIV-1 infection in women. Nanoscale. 2017 Jul 13; 9(27):9732-9742. IF: 7,367 (1st Decilee). G2-S16 dendrimer is an ideal candidate for development a topical microbicide against HIV-1 and the next step is try in clinical trials.

1.-Felipe García, business name of Research Performing Institution (IDIBAPS). We have closely collaborated more that 15 years in the development of vaccine and microbicides against HIV-1 infection, in the field of nanotechnology and we have published in collaboration more than 10 articles.​

2.-J Pierre Majoral & PhD L Peng, Research Director CNRS, Laboratoire de Chimie de Centre National Recherche Scientifique/France. Biological Applications of Dendrimers

3.-Dietmar Appelhans, Head of the Department of Bio-active and Responsive Polymers/Leibniz lnstitute of Polymer Research/Germany. Synthesis and Biological Applications of Dendrimers.

4.-Dzimitry Scharbin, Institute of Biophysics and Cell Engineering of the National Academy of Sciences of Belarus/Belarus. Biophysical Characterization of Dendrimers.

5.-Marek Maly, Faculty of Science/J.E. Purkinje University in Usti nad Labem/Czech Republic. Computer modeling of interaction between dendrimers and biological targets.