Nanotechnology in HIV Treatment: Targeting Reservoirs

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AIDS is one of the greatest evils that the entire world has been struggling to deal with, even up to date; the number of people affected by the disease is in the millions. Even though present-day ART has been able to successfully control viral copy production to the point where it cannot be measured, there is no cure for HIV. Among the factors that define it, one must mention the presence of the viral reservoirs that are concealed deep in the organism. These are cells and tissues where the virus can lay dormant and not be detected by the immune system, or ART. Contemporary progress achieved in the field of nanotechnology opens new possibilities to hit these reservoirs more efficiently, which could lead to further treatment and even the eradication of HIV. This article looks into the opportunities that nanotechnology brings to the containment and eradication of HIV reservoirs.

Understanding HIV Reservoirs

HIV reservoirs are mainly composed of cells with a long life span that host HIV in a dormant state. These reservoirs are located in different tissues of the body, such as the brain, lymph nodes, GALT, and blood. The virus in these reservoirs can remain latent for years and may reactivate if the ART is stopped. This latency is a major problem for the treatment because standard ART has only eradicated the parts of the HIV that are actively dividing and reproducing but cannot do so for the dormant stratum. 

The generation and sustenance of such reservoirs are induced by the following: Initially, HIV dissociates and becomes integrated into the host’s DNA to exist as a provirus genome. This integration lets the virus avoid detection by the immune system of the host. Second, the reservoirs are usually harbored in immune-privileged areas where immune detection is low, for instance, the brain. Third, the virus can infect long-lived cells, including memory CD4+ T cells that have a relatively long life span and can be kept latent for long periods.

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Current ART regimens are effective at suppressing HIV replication, but they have several limitations when it comes to eradicating the virus from reservoirs: Modern approaches to the usage of ART are characterized by satisfactory results achieved in controlling viral replication, but they have certain drawbacks in terms of the virus eradication from the source:

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Limited Penetration

However, by the same token, some of the anti-retroviral drugs have been established to be incapable of penetrating the blood-cerebrospinal barrier to be able to access the areas where reservoirs are usually established.

Drug Toxicity

The patients’ quality of life is consequently impacted due to toxicity and further side effects when on long-term ART.

Drug Resistance

The virus can acquire drug resistance, mainly if patient compliance with the prescribed therapy is not optimal.

Latent Infection

ART is rather useless in eliminating latent viruses since the virus is dormant and does not produce new virions.

It entails that the eradication of the virus from these reservoirs has not been achieved; hence, patients will require ART for life. Even therapy can be interrupted, and as a result, viral replication resumes and a relapse of the infection occurs. This therefore speaks volumes about the need for approaches that would be effective in eradicating the said reservoirs.

Nanotechnology-Based Approaches

Nanotechnology has some brilliant approaches to these problems through effective delivery of drugs, cell selectivity, and the effectiveness of HIV medications.

Nanocarriers for Drug Delivery

Liposomes, nanoparticles, and dendrimers can have antiretroviral drugs incorporated into their structure, thus protecting the drugs from degradation and directing them to the target tissue. These nanocarriers can be created specifically to carry the drugs across barriers, for example, the blood-brain barrier, and to maximize drug penetration into the reservoirs that are in the brain.

For instance, nano-sized carriers made from polymers have been used to a considerable extent in drug delivery to tissues that have been hard to reach. These nanocarriers can be made to control the rate of releasing their content at the site of action, so the frequency of drug delivery can be reduced and side effects eliminated.

Some research has revealed the possibilities of lipid-based nanoparticles for increasing antiretroviral drug delivery across the blood-brain barrier. REM has been used for the delivery of several drugs across the blood-brain barrier by altering the nanoparticle surface with targeting ligands and enhancing the nanoparticle uptake by the brain cells, thus enhancing the concentration of the drugs in the brain. To date, early studies on the use of this approach have been demonstrated in preclinical models, with the investigators now implementing clinical trials.

Targeted Nanotherapy

Targeted nanotherapy can be done by having nanocarriers functionalized with certain ligands or antibodies to home in on nanocarrier cells. This targeting can enhance drug accumulation in infected cells while keeping non-infected cells unharmed, thus lowering toxicity.

It has also been established that nanoparticles coated with ligands that have an affinity for HIV-infected cells’s CD4 or CCR5 receptors can target these cells for the release of the antiviral drug. This targeted approach increases the effectiveness of the drugs as well as reduces the side effects associated with them.

For instance, a current study illustrated how major tranquilizers temporarily altered the typography of the governing subsists by employing antibody-conjugated nanoparticles to guide antiretroviral drugs to HIV-infected cells. They were functionalized with antibodies that bind to a protein on the surface of the infected cells, thereby allowing the drug to be selectively delivered to the specific cells. Fortified by increased permeability, this approach also decreased the toxicity of the drug to the non-infected cells.

Combination Nanotherapy

Coadministration of different drugs with the aid of one nanocarrier can have a complementary impact that is positive for the overall therapeutic efficacy. This approach may involve the use of standard antiretroviral therapy in conjunction with LRAs that wake up latent HIV, making it vulnerable to CD4 cells and antiretroviral treatment.

These agents can be incorporated into nanocarriers, which could deliver them ratio-wise, activating latent viruses and eliminating them with the help of antiretroviral drugs.

One of the potential approaches is the employment of nanoparticles for the administration of an antiretroviral drug in association with an LRA. The LRA brings the virus to future recognition by the immune system; it marks the virus, making it within reach of the antiretroviral drug. This combination approach has been found useful in preclinical studies since it has been shown to lessen the viral reservoir as well as poise the viral recurrence after ART interruption.

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Nanovaccines

Nanotechnology is also being used in research related to HIV vaccines. Nanovaccines can expose the body to HIV antigens in a way that is most like a natural infection, which results in a strong response. These vaccines can be developed to elicit both antibody and cell-mediated immunity, giving a strong anti-HIV defense.

For example, nanoparticles can be employed for the delivery of DNA or RNA vaccines that, in turn, encode the antigens of HIV, resulting in an effective immune response. These vaccines can be made to target specific dendritic cells that form the functional link between immune system stimulants and the immune response.

Current research shows the efficacy of lipid nanoparticles as carriers of a vaccine based on mRNA encoding HIV antigens. It also triggered in the animal models the generation of neutralizing antibodies and the killing of the infected cells through cytotoxic T cells. In this case, the strategy is being tested in clinical trials to extend immunity to HIV.

Application to Clinical Practice and Research Directions

Nanotechnology indeed shows a great prospect in HIV treatment; however, several barriers should be overcome to successfully apply nanotechnology in clinical practice.

Safety and Toxicity

The chronic stability and possibility of toxicity of nanocarriers also have to be investigated. Even though many nanocarriers are developed to possess biocompatibility, their effects on the immune system and toxic effects should be investigated.

The safety of nanocarriers can, however, vary with their size and shape, the chemistry used to coat the surface, and even the type of materials used in their construction. At the same time, scholars are designing nanocarriers by using biodegradable and biocompatible materials to avoid risks. Also, more complex approaches are employed for the assessment of the relationship between forms of nanocarriers and the immune system, focusing on the absence of undesirable immune reactions.

Manufacturing and Scalability

Larger-scale synthesis of nanocarriers and maintaining uniform and efficient production are very difficult. Enhancements in the manufacturing process are required to make these therapies reproducible while at the same time reducing costs.

Production of nanocarriers on a large scale entails standardizing the techniques of synthesis to work with identical results. This includes issues about the size and surface characteristics of the nanocarriers, the issues viewed with consistency in the drug loading, and its subsequent release. There are equal efforts made by the researchers to employ impact-opposed and high-volumetric manufacturing structures and technologies to manufacture food supplements efficiently.

Regulatory Approval

Because of the nature of nanotechnology, these therapies should be strictly monitored, regulated, and approved before they are dispensed to patients. Thus, this has raised the need for policies on how to evaluate these therapies so that they can be recommended and embraced.

Currently, the American FDA and the European EMA agencies are working on future guidelines for the assessment of nanotherapies. Such guidelines are available in the following areas of nanomedicine: pre-clinical, clinical, and production. The current and prospective manufacturers and researchers dealing with nanomedicines practicing cross-cutting need to treat with statutory bodies to make sure the nanomedicines developed are up to the required standards.

Patient Acceptance

 Due to political pressure and healthcare policymaking, patient acceptance is critical to new therapies’ effectiveness. Awareness-creation campaigns ought to be developed to enlighten the patients on the effectiveness of the nanotechnology treatment and its possible dangers.

This paper posits that for nanotechnology-based therapies to gain recognition and acceptance within society, there is a need to involve and educate the patients as well as the healthcare providers. This also means making available and easily understandable pertinent information on the advantages of such treatments and the possible drawbacks to dispel myths or bother a patient. Several patient associations and community-based organizations can help spread information and empower patients to choose the best management plan.

Conclusion

Thus, it can be concluded that nanotechnology has a unique potential for HIV infection treatment and may help to overcome the existing strategies to eliminate viral reservoirs. Nanotechnology for HIV/AIDS can actively address the imperatives of antiretroviral treatments by increasing drug delivery, the specificity of targeting, and combination therapy. Further investigation in this area and rigorous assessment of safety and effectiveness will be instrumental, as they would contribute to the implementation of these novel strategies in the clinical setting, thus progressing towards the vision of an HIV-free world.

Namely, nanotechnology does not only offer refinements of the existing treatments but even more. It creates opportunities for completely different therapeutic approaches that will be able to fight HIV better. For example, science investigates the possibility of using nanotechnology in the creation of advanced devices assisting in gene modification, including the well-known CRISPR/Cas9 system, which is widely used to accurately locate the viral genetic material in the affected cells and then remove it. Further, the incorporation of nanotechnology could help in the deployment of needs- and trait-specific medicine solutions, implying that medical solutions are delivered depending on the patient’s needs and profile.

References

  1. Dutt, Y., Pandey, R.P., Dutt, M., Gupta, A., Vibhuti, A., Raj, V.S., Chang, C.M. and Priyadarshini, A., 2023. Silver nanoparticles phytofabricated through Azadirachta indica: anticancer, apoptotic, and wound-healing properties. Antibiotics, 12(1), p.121.
  2. Kong, C. and Chen, X., 2022. Combined photodynamic and photothermal therapy and immunotherapy for cancer treatment: a review. International journal of nanomedicine, 17, p.6427.
  3. Yan N, Xu J, Liu G, Ma C, Bao L, Cong Y, Wang Z, Zhao Y, Xu W, Chen C. Penetrating Macrophage-Based Nanoformulation for Periodontitis Treatment. ACS Nano. 2022 Nov 22;16(11):18253-18265. doi: 10.1021/acsnano.2c05923. Epub 2022 Oct 26. PMID: 36288552.
  4. Ahmad Shariff SH, Wan Abdul Khodir WK, Abd Hamid S, Haris MS, Ismail MW. Poly(caprolactone)-b-poly(ethylene glycol)-Based Polymeric Micelles as Drug Carriers for Efficient Breast Cancer Therapy: A Systematic Review. Polymers (Basel). 2022 Nov 10;14(22):4847. doi: 10.3390/polym14224847. PMID: 36432974; PMCID: PMC9698711.
  5. Zhao Y, Liu X, Liu X, Yu J, Bai X, Wu X, Guo X, Liu Z, Liu X. Combination of phototherapy with immune checkpoint blockade: Theory and practice in cancer. Front Immunol. 2022 Sep 2;13:955920. doi: 10.3389/fimmu.2022.955920. PMID: 36119019; PMCID: PMC9478587.
  6. Tan G, Wang L, Pan W, Chen K. Polysaccharide Electrospun Nanofibers for Wound Healing Applications. Int J Nanomedicine. 2022 Sep 6;17:3913-3931. doi: 10.2147/IJN.S371900. PMID: 36097445; PMCID: PMC9464040.
  7. Fotooh Abadi, L., Damiri, F., Zehravi, M., Joshi, R., Pai, R., Berrada, M., Massoud, E.E.S., Rahman, M.H., Rojekar, S. and Cavalu, S., 2022. Novel nanotechnology-based approaches for targeting HIV reservoirs. Polymers, 14(15), p.3090.