Biological Obstacles Research Articles

Advancements in mitochondrial-targeted nanotherapeutics: overcoming biological obstacles and optimizing drug delivery

In recent decades, nanotechnology has significantly advanced drug delivery systems, particularly in targeting subcellular organelles, thus opening new avenues for disease treatment. Mitochondria, critical for cellular energy and health, when dysfunctional, contribute to cancer, neurodegenerative diseases, and metabolic disorders. This has propelled the development of nanomedicines aimed at precise mitochondrial targeting to modulate their function, marking a research hotspot. This review delves into the recent advancements in mitochondrial-targeted nanotherapeutics, with a comprehensive focus on targeting strategies, nanocarrier designs, and their therapeutic applications. It emphasizes nanotechnology’s role in enhancing drug delivery by overcoming biological barriers and optimizing drug design for specific mitochondrial targeting. Strategies exploiting mitochondrial membrane potential differences and specific targeting ligands improve the delivery and mitochondrial accumulation of nanomedicines. The use of diverse nanocarriers, including liposomes, polymer nanoparticles, and inorganic nanoparticles, tailored for effective mitochondrial targeting, shows promise in anti-tumor and neurodegenerative treatments. The review addresses the challenges and future directions in mitochondrial targeting nanotherapy, highlighting the need for precision, reduced toxicity, and clinical validation. Mitochondrial targeting nanotherapy stands at the forefront of therapeutic strategies, offering innovative treatment perspectives. Ongoing innovation and research are crucial for developing more precise and effective treatment modalities.

"Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability".

The oral route stands out as the most commonly used method for drug administration, prized for its non-invasive nature, patient compliance, and easy administration. Several elements influence the absorption of oral medications, including their solubility, permeability across mucosal membranes, and stability within the gastrointestinal (GI) environment. Research has delved into comprehending physicochemical, biochemical, metabolic, and biological obstacles that impact the bioavailability of a drug. To improve oral drug absorption, several pharmaceutical technologies and delivery methods have been studied, including cyclodextrins, micelles, nanocarriers, and lipid-based carriers. This review examines both traditional and innovative drug delivery methods, as well as the physiological and pharmacological barriers influencing medication bioavailability when taken orally. Additionally, it describes the challenges and advancements in developing formulations suitable for oral use.

Challenges faced by spotted seals born in captivity and released into the wild

The artificial reproduction of endangered marine species populations is becoming increasingly crucial. Determining the potential for reintegration into their natural ecological niche remains a persistent obstacle in conservation biology. Spotted seals (Phoca largha) are a flagship species in the Chinese marine ecosystem. Efforts have been made to artificially breed them to prevent local extinction. Our study monitored 18 captive-born (nine) and rehabilitated (nine) individuals released into the Bohai Sea between 2010 and 2020. We examined the ecological niche-seeking behavior of captive-born seals (CS) using rehabilitated wild seals (RS) as benchmarks. It encompassed three oceanic gradients, habitat patterns, and potential threats. The findings demonstrated that CS did not return to the appropriate latitudes, horizontals, and sea surface salinity gradients in the ocean. Despite a larger potential habitat area for CS, it exhibited high temporal variability (with an average monthly fluctuation of 53 %) and demonstrated limited spatial overlap with the RS habitat (27 % overlap in July), and four indices, including the Splitting and Global Moran's Indices indicated a higher level of habitat fragmentation. Additionally, the number of shipping hotspots and collision risk within the CS habitats were twice those of the RS. These findings suggest that the released CS did not fully integrate into its native ecological niche. Our objective is to offer a pragmatic approach and framework for monitoring and assessing marine species released into the ocean.

(Invited) Carbon Nanodots for Improved Plant Genetic Engineering

Anthropogenic climate change has made the need for more nutritious and stress-tolerant plants indisputable for providing food security. Climate change has decreased the global agricultural productivity by 21% since 1961, and will continue to drop crop yields by 7.4% for every degree-Celsius increase in temperature. CRISPR genetic engineering can enable previously inaccessible crop tolerances to meet the demand for nutritionally-balanced and high-yielding crops. However, plant biomolecule delivery and transformation are two important bottlenecks that prevent plant genetic engineering from reaching its full potential.Nanomaterials have already shown promise to deliver genetic cargoes into plant somatic cells for transient expression of proteins1. For most applications in agriculture, however, biomolecules need to be delivered to cells that can give rise to next generation of edited plants, such as germ or stem cells. These cell types are extremely challenging to penetrate and deliver cargoes using traditional approaches, hence forcing researchers to use undifferentiated tissues to transform and go through an arduous regeneration process in tissue culture. This time consuming, inefficient, and highly species dependent approach has been a critical obstacle in plant biology and bioengineering.We have synthesized small (~3 nm) and positively charged (+35 mV) carbon nanodots (CNDs) from glycerol and polyethyleneimine (PEI) using the microwave method. These CNDs showed high entry efficiency into plant stem cells and ability to deliver DNA cargoes into a model plant Nicotiana benthamiana without affecting stem cell viability and differentiation capability. This is a first-time demonstration of nanoparticle uptake by plant stem cells and cargo expression in these cell types. Once we perform CRISPR gene editing in these stem cells, the edited germ cells and seeds will develop automatically from the stem cells, facilitating the creation of edited and improved new plant varieties.

Nanoparticle-Mediated Mucosal Vaccination: Harnessing Nucleic Acids for Immune Enhancement.

Recent advancements in in vitro transcribed mRNA (IVT-mRNA) vaccine manufacturing have attracted considerable interest as advanced methods for combating viral infections. The respiratory mucosa is a primary target for pathogen attack, but traditional intramuscular vaccines are not effective in generating protective ion mucosal surfaces. Mucosal immunization can induce both systemic and mucosal immunity by effectively eliminating microorganisms before their growth and development. However, there are several biological and physical obstacles to the administration of genetic payloads, such as IVT-mRNA and DNA, to the pulmonary and nasal mucosa. Nucleic acid vaccine nanocarriers should effectively protect and load genetic payloads to overcome barriers i.e., biological and physical, at the mucosal sites. This may aid in the transfection of specific antigens, epithelial cells, and incorporation of adjuvants. In this review, we address strategies for delivering genetic payloads, such as nucleic acid vaccines, that have been studied in the past and their potential applications.

Review of Oral Tablet

Abstract: Oral drug delivery is noninvasive, has a high rate of patient compliance, is easy to handle, and doesn't require any special sterile settings, it is the most popular method of administration. Nevertheless, a number of physical, biological, and pharmacological obstacles that certain medications must overcome in order to be absorbed into the systemic circulation reduce their therapeutic efficiency. The use of nanocarriers to deliver drugs orally has proven to be an effective solution to the aforementioned problems and is being explored as a potential replacement for oral medication administration. This chapter provides an overview of the latest developments in the use of nanocarriers for oral medication delivery in the treatment of different disorders. The chapter also describes how diverse nanocarrier designs and technologies improve therapeutic potential by overcoming physical, biological, and biochemical obstacles. it is easy to produce, has few sterility limitations, is less expensive, has flexible dosage form design, and has high patient compliance, oral drug delivery (ODD) is the most convenient and favored method of drug administration. However, low medication bioavailability—which is influenced by three crucial factors—is one of the difficulties associated with oral drug delivery. The other is solubility. Many mathematical models that predict the medication's rate of solubility and dissolution have been developed in order to achieve efficient drug absorption in vivo. Similarly, models that are noncellular and cellular determine permeability. Furthermore, the medication's behavior in the gastrointestinal tract (GIT) is influenced by physiological parameters, such as pH, microbial colonization, and enzymes, as well as intrinsic drug properties. A drug's dosage form is a method of getting it into a living organism. The medicine must be administered to the site of action at a rate and concentration that will maximize therapeutic benefit and minimize side effects in order to provide the intended result. Although the oral method is still commonly used, swallowing tablets and capsules can be a regular problem. As a result, numerous studies on cutting-edge drug delivery methods have been conducted. This review focuses on oral dispersible tablets, a novel approach to drug delivery systems that are currently more focused on formulation and set a new course that not only helped patients increase their level of therapy compliance.

Social and biological innovations are essential to deliver transformative forest biotechnologies.

Forests make immense contributions to societies in the form of ecological services and sustainable industrial products. However, they face major challenges to their viability and economic use due to climate change and growing biotic and economic threats, for which recombinant DNA (rDNA) technology can sometimes provide solutions. But the application of rDNA technologies to forest trees faces major social and biological obstacles that make its societal acceptance a 'wicked' problem without straightforward solutions. We discuss the nature of these problems, and the social and biological innovations that we consider essential for progress. As case studies of biological challenges, we focus on studies of modifications in wood chemistry and transformation efficiency. We call for major innovations in regulations, and the dissolution of method-based market barriers, that together could lead to greater research investments, enable wide use of field studies, and facilitate the integration of rDNA-modified trees into conventional breeding programs. Without near-term adoption of such innovations, rDNA-based solutions will be largely unavailable to help forests adapt to the growing stresses from climate change and the proliferation of forest pests, nor will they be available to provide economic and environmental benefits from expanded use of wood and related bioproducts as part of an expanding bioeconomy.

Exploring the Potential of Nanoparticles in the Treatment of Breast Cancer: Current Applications and Future Directions

Breast cancer (BC) ranks among the most diagnosed solid tumors worldwide. For decades, significant research efforts have been dedicated to finding selective treatments for these solid tumors. Currently, the primary treatment method for BC involves surgery, with the subsequent utilization of radiotherapy and chemotherapy. However, these subsequent treatments often fall short of effectively treating BC due to their side effects and harm to healthy tissues. Today, a range of nanoparticles are being developed to target BC cells without affecting the surrounding healthy tissues. This in-depth review, based on studies, seeks to shed light on these specially designed nanoparticles and their potential in BC treatment. Typically, therapeutic drugs or naturally occurring bioactive compounds are incorporated into precisely crafted nanoparticles. This enhances their solubility, longevity in the bloodstream, and distribution in the body while also minimizing side effects and immune reactions. Nanoparticles have been designed to address the shortcomings of standalone therapeutics and traverse various biological obstacles spanning the systemic, microenvironmental, and cellular that differ among patients and diseases. We prioritize breakthroughs in nanoparticle design to surpass diverse delivery obstacles and believe that smart nanoparticle engineering not only enhances effectiveness for general delivery but also allows customized solutions for specific needs, ultimately leading to better outcomes for patients.

Navigating the brain: the role of exosomal shuttles in precision therapeutics.

Brain diseases have become one of the leading roots of mortality and disability worldwide, contributing a significant part of the disease burden on healthcare systems. The blood-brain barrier (BBB) is a primary physical and biological obstacle that allows only small molecules to pass through it. Its selective permeability is a significant challenge in delivering therapeutics into the brain for treating brain dysfunction. It is estimated that only 2% of the new central nervous system (CNS) therapeutic compounds can cross the BBB and achieve their therapeutic targets. Scientists are exploring various approaches to develop effective cargo delivery vehicles to promote better therapeutics targeting the brain with minimal off-target side effects. Despite different synthetic carriers, one of the natural brain cargo delivery systems, "exosomes," are now employed to transport drugs through the BBB. Exosomes are naturally occurring small extracellular vesicles (EVs) with unique advantages as a therapeutic delivery system for treating brain disorders. They have beneficial innate aspects of biocompatibility, higher stability, ability to cross BBB, low cytotoxicity, low immunogenicity, homing potential, targeted delivery, and reducing off-site target effects. In this review, we will discuss the limitations of synthetic carriers and the utilization of naturally occurring exosomes as brain-targeted cargo delivery vehicles and highlight the methods for modifying exosome surfaces and drug loading into exosomes. We will also enlist neurodegenerative disorders targeted with genetically modified exosomes for their treatment.

The Biological and Clinical Role of the Telomerase Reverse Transcriptase Gene in Glioblastoma: A Potential Therapeutic Target?

Glioblastoma IDH-wildtype represents the most lethal and frequent primary tumor of the central nervous system. Thanks to important scientific efforts, we can now investigate its deep genomic assessment, elucidating mutated genes and altered biological mechanisms in addition to its clinical aggressiveness. The telomerase reverse transcriptase gene (TERT) is the most frequently altered gene in solid tumors, including brain tumors and GBM IDH-wildtype. In particular, it can be observed in approximately 80-90% of GBM IDH-wildtype cases. Its clonal distribution on almost all cancer cells makes this gene an optimal target. However, the research of effective TERT inhibitors is complicated by several biological and clinical obstacles which can be only partially surmounted. Very recently, novel immunological approaches leading to TERT inhibition have been investigated, offering the potential to develop an effective target for this altered protein. Here, we perform a narrative review investigating the biological role of TERT alterations on glioblastoma and the principal obstacles associated with TERT inhibitions in this population. Moreover, we discuss possible combination treatment strategies to overcome these limitations.

A review on emerging herbal nanotechnology for skin cancer

Many phytochemicals such as tannins, terpenoids and flavonoids are hydrophilic in nature, but have low absorption, because they are unable to cross lipid membranes of cells. It has been proposed to combine phytomedicine to nanotechnology, because nanocarrier can deliver active phytochemical during entire treatment period, directing it to the desired site of action. The main aim of this work is to review Phytochemicals which possess promising anti-carcinogenic capabilities in a variety of skin cancer cell lines, animal models and their mechanism of action. The commercial formulations for skin cancer prevention and therapy that are now on the market that is derived from plants are also covered in this review. This paper focused on the recent assessment of the biological obstacles to topical applications of phytoconstituents and also focuses on review of the enormous potential for bioactive phytochemical distribution via developing nanotechnology.

Nanotheranostics: Platforms, Current Applications, and Mechanisms of Targeting in Breast and Prostate Cancers

Globally, cancer is one of the deadliest diseases, needing a meticulous diagnosis and targeted treatment plan to achieve an initial prognosis, followed by precision and optimization in treatment. Nonselective targeting, difficulty in accurately monitoring treatment end-results, serious drug side-effects, and severity of disease resulting in metastasis are the key flaws of traditional techniques. Nanotechnology and nanoparticles possess special features to completely transform the field of diagnosis and treatment of cancer. A holistic strategy that employs a dual function of diagnosis and therapy while utilizing a nanocarrier is referred to as a nanotheranostic. The nanotheranostic framework was created to surmount a variety of biological and physiological obstacles, effectively delivering the cargo to the intended target location, while simultaneously facilitating therapeutic intervention, surveillance, and validation to demonstrate improved treatment effectiveness. As a result, a nanotheranostic platform can be useful for targeted drug delivery, release, and distribution assessment, in addition to patient classification and survival. Nanotheranostic techniques also lead to reduced drug side-effects compared with conventional therapies. In this review, we outline current studies on nanotheranostics and their advantages over conventional treatment strategies, the applications and challenges/limitations of nanotheranostics, and the mechanisms of targeting in breast and prostate cancers.

A chemoimmunotherapy-based strategy to enhance tumor therapy by cross-linking a novel size-variable nanocluster via a bifunctional peptide

The combination of chemotherapy and immunotherapy plays a synergistic role in improving the effectiveness of cancer treatment. However, it is a great challenge to deliver drugs accurately and efficiently to the target and exert synergistic effects due to multiple biological obstacles in vivo. Here, we constructed a novel size-variable three-dimensional mesh nanocluster (HA/P-A cluster) cross-linked by bifunctional peptide R14 for tumor targeted co-delivery of doxorubicin (DOX) and pPD-L1 trap. The ERP effect and the targeting effect of the outer layer of HA synergistically mediated the accumulation of nanoclusters in tumor tissues. Subsequently, R14 was broken by matrix metalloproteinase-2 (MMP-2) and the nanoclusters (180 nm) were cleaved into ultra-small size nanoparticles (∼10 nm), achieving deep penetration while targeting tumor cells through RGD at both ends of R14. Based on this strategy, DOX acts as an initiator to induce immunogenic cell death (ICD) while immunodrugs block the PD-L1 pathway. Both in vitro and in vivo studies have shown that HA/P-A cluster effectively retarded tumor growth. Moreover, HA/P-A cluster treatment resulted in a significant increased CD8+ T cell infiltration in tumor tissue. In conclusion, this strategy provides a new direction for targeted co-delivery of nanoplatforms to improve chemoimmunotherapy in solid tumors.

Epidemiological Characteristics of Generalized COVID-19 Deterministic Disease Model

Coronavirus disease 2019 (COVID-19) is an infection that can result in lung issues such as pneumonia and, in extreme situations, the most severe acute respiratory syndrome. COVID-19 is widely investigated by researchers through mathematical models from different aspects. Inspired from the literature, in the present paper, the generalized deterministic COVID-19 model is considered and examined. The basic reproduction number is obtained which is a key factor in defining the nonlinear dynamics of biological and physical obstacles in the study of mathematical models of COVID-19 disease. To better comprehend the dynamical behavior of the continuous model, two unconditionally stable schemes, i.e., mixed Euler and nonstandard finite difference (NSFD) schemes are developed for the continuous model. For the discrete NSFD scheme, the boundedness and positivity of solutions are discussed in detail. The local stability of disease-free and endemic equilibria is demonstrated by constructing Jacobian matrices for NSFD scheme; nevertheless, the global stability of aforementioned equilibria is verified by using Lyapunov functions. Numerical simulations are also presented that demonstrate how both the schemes are effective and suitable for solving the continuous model. Consequently, the outcomes obtained through these schemes are completely according to the solutions of the continuous model.

Pluripotent Stem Cell-Derived In Vitro Gametogenesis and Synthetic Embryos-It Is Never Too Early for an Ethical Debate.

Recently, 2 branches of the wide area of synthetic biology-in vitro gametogenesis and synthetic embryo development-have gained considerable attention. Rodent induced pluripotent stem cells derived via reprogramming of somatic cells can in vitro be differentiated into gametes to produce fertile offspring. And even synthetic embryos with organ progenitors were generated ex utero entirely from murine pluripotent stem cells. The use of these approaches in basic research, which is rightfully accompanied by an ethical discussion, will allow hitherto unattainable insights into the processes of the beginning of life. There is a broad international consensus that currently the application of these technologies in human-assisted reproduction must be considered to be unsafe and unethical. However, newspaper headlines also addressed the putatively resulting paradigm shift in human reproduction and thereby raised expectations in patients. Due to unsolved biological and technological obstacles, most scientists do not anticipate translation of any of these approaches into human reproductive medicine, if ever, for the next 10 years. Still, whereas the usage of synthetic embryos for reproductive purposes should be banned, in the context of in vitro-derived human gametes it is not too early to initiate the evaluation of the ethical implications, which could still remain assuming all technological hurdles can ever be cleared.

Flowing through Gastrointestinal Barriers with Model Nanoparticles: From Complex Fluids to Model Human Intestinal Epithelium Permeation.

Most nanomaterial-based medicines are intravenously applied since oral administration comprises challenging-related biological obstacles, such as interactions with distinct digestive fluids and their transport through the intestinal barrier. Moreover, there is a lack of nanoparticle-based studies that faithfully consider the above-cited obstacles and boost oral-administered nanomedicines' rational design. In this study, the physicochemical stability of fluorescent model silica nanoparticles (f-SiO2NPs) passing through all simulated gastrointestinal fluids (salivary, gastric, and intestinal) and their absorption and transport across a model human intestinal epithelium barrier are investigated. An aggregation/disaggregation f-SiO2NPs process is identified, although these particles remain chemically and physically stable after exposure to digestive fluids. Further, fine imaging of f-SiO2NPs through the absorption and transport across the human intestinal epithelium indicates that nanoparticle transport is time-dependent. The above-presented protocol shows tremendous potential for deciphering fundamental gastrointestinal nanoparticles' evolution and can contribute to rational oral administration-based nanomedicine design.

Ethiopian Plasmodium vivax hypnozoites formation dynamics and their susceptibility to reference antimalarial drugs

One of the key obstacles to malaria elimination is largely attributed to Plasmodium vivax’s ability to form resilient hypnozoites in the host liver that cause relapsing infections. As a result, interruption of P. vivax transmission is difficult. P. vivax transmission occurs in Duffy-positive individuals and have been mainly thought to be absent in Africa. However, increasing studies using molecular tools detected P. vivax among Duffy-negative individuals in various African countries. Studies on the African P. vivax has been severely limited because most of malaria control program focus mainly on falciparum malaria. In addition, there is a scarcity of laboratory infrastructures to overcome the biological obstacles posed by P. vivax. Herein, we established field transmission of Ethiopian P. vivax for routine sporozoite supply followed by liver stage infection in Mali. Furthermore, we evaluated local P. vivax hypnozoites and schizonts susceptibilities to reference antimalarial drugs. The study enabled the assessment of local African P. vivax hypnozoite production dynamics. Our data displayed the ability of the African P. vivax to produce hypnozoite forms ex-vivo at different rates per field isolate. We report that while tafenoquine (1µM) potently inhibited both hypnozoites and schizont forms; atovaquone (0.25µM) and the phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691 (0.5µM) showed no activity against hypnozoites forms. Unlike hypnozoites forms, P. vivax schizont stages were fully susceptible to both atovaquone (0.25µM) and the (PI4K)-specific inhibitor KDU691 (0.5µM). Together, the data revealed the importance of the local platform for further biological investigation and implementation of drug discovery program on the African P. vivax clinical isolates.

Weed biological control with fungi-based bioherbicides

Biological control refers to the use of living beneficial organisms as well as the products of their metabolism in pest control. Weed plants are indispensable companions of cultivated plants, in which they cause substantial damage. Organic food production, human health care and environmental preservation impose a need for the production and application of bioherbicides, particularly in organic systems of plant production. Plant pathogens have significant potential as biological agents in weed control. The aim of the present study was to indicate the most important properties of the weed biological control system, with particular emphasis on the use of fungi-based bioherbicides. According to the organism they suppress, biopesticides are classified into bioinsecticides, biofungicides, bioherbicides, etc. Weed control using plant pathogens can be performed in three ways, by classical, conservation and augmentative biological control. Bioherbicides were initially introduced to the market in 1980, and the majority of them were fungi-based bioherbicides. The most common fungi included in bioherbicides belong to the genera Alternaria, Colletotrichum, Cercospora, Fusarium, Phomopsis, Phytophthora, Phoma, Puccinia, etc. The studies, development and final commercialisation of fungi as biological control agents face many obstacles, ranging from basic biological facts to social and economic factors. There are also challenges in the production, formulation process, environmental friendliness, duration of herbicidal action, and expensive and time-consuming registration procedures. Considering the success in weed suppression with fungi-based bioherbicides, the global market is still dominated by chemical companies manufacturing synthetic herbicides, while there are no such products on the Serbian market yet.

Plant Microbiome Engineering: Hopes or Hypes.

Rhizosphere microbiome is a dynamic and complex zone of microbial communities. This complex plant-associated microbial community, usually regarded as the plant's second genome, plays a crucial role in plant health. It is unquestioned that plant microbiome collectively contributes to plant growth and fitness. It also provides a safeguard from plant pathogens, and induces tolerance in the host against abiotic stressors. The revolution in omics, gene-editing and sequencing tools have somehow led to unravel the compositions and latent interactions between plants and microbes. Similarly, besides standard practices, many biotechnological, (bio)chemical and ecological methods have also been proposed. Such platforms have been solely dedicated to engineer the complex microbiome by untangling the potential barriers, and to achieve better agriculture output. Yet, several limitations, for example, the biological obstacles, abiotic constraints and molecular tools that capably impact plant microbiome engineering and functionality, remained unaddressed problems. In this review, we provide a holistic overview of plant microbiome composition, complexities, and major challenges in plant microbiome engineering. Then, we unearthed all inevitable abiotic factors that serve as bottlenecks by discouraging plant microbiome engineering and functionality. Lastly, by exploring the inherent role of micro/macrofauna, we propose economic and eco-friendly strategies that could be harnessed sustainably and biotechnologically for resilient plant microbiome engineering.

Enhancing the Anti-Hepatocarcinoma Efficacy of Cytokine Induced Killer Cells by TLS11a-Lipo-hENG scFv/hIP-10 Nanocapsules

Developing a novel therapeutic approach to prevent and treat hepatocellular carcinoma (HCC) is essential. As an adoptive cell therapy candidate, cytokine-induced killer (CIK) cell immunotherapy is ideal. However, for efficacy in vivo delivery of CIK cells conjugate with antibody antineoplastic agents into the cancer cells, various biological obstacles including rapid degradation in vivo and the absence of active targeting capability need to be overcome. Previously, we developed a fusion antibody-chemokine protein which contained human Endoglin antibodies and human Interferon-gamma-induced protein 10 (hENG scFv/hIP-10). To this end, we present that a novel synthesized TLS11a-Lipo-hENG scFv/hIP-10 nanocapsules, which combine the advantages of prolonged half-life and good stability liposomes and HCC-specific targeting aptamer “TLS11a,” would be able to realize efficient and effective in vivo therapy. Also, we find that in combination with CIK cells possess a greater anti-hepatocarcinoma efficacy. Combined with TLS11a-Lipo-hENG scFv/hIP-10 nanocapsules and CIK cells, they could suppress tumor growth and prolong the survival of hepatoma-bearing mice through recruiting endogenous CIK cells in tumor tissues, inhibiting cell proliferation in tumors while promoting apoptosis and producing IFN-γ level. It appears that TLS11a-Lipo-hENG scFv/hIP-10 nanocapsules can enhance the antitumor activity of CIK cells against human hepatocellular carcinoma.