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NML Review | University of Nirma: Nano-biological Carriers for Lung Cancer Management

The incidence of cancer is rising globally. Lung cancer is considered to be one of the deadliest forms of cancer, with complex clinical effects and poor prognosis. Nano-bioengineering is an applied science. Through the design of new nano-biological tools and strategies, it can assist in the clinical treatment and innovate the diagnosis of lung cancer. Nano-bioengineering has currently studied many new types of bio-nano devices and expanded their applications to radiation therapy, immunotherapy, phototherapy, gene therapy, and combination therapy, as well as new therapies that promote multi-modal tumor targeting for lung cancer. The search for suitable targeted treatment strategies has also led to the development of new types of nanocarriers called "nanobiological carriers". Among them, nano-biological carriers are mostly bio-engineered, bionic, bio-sourced and bio-mixed nano-carriers, cells or vesicles. Different from other nano-carriers, nano-biological carriers have obvious advantages such as multiple targets, high biological interaction, strong biocompatibility, inherent camouflage and scalability.


Bio-Nanocarriers for Lung Cancer Management: Befriending the Barriers
Shruti Rawal, Mayur Patel*
Nano-Micro Letters (2021)13: 142
https://doi.org/10.1007/s40820-021-00630-6

Highlights of this article
1. The review introduces the factors that affect the prognosis of lung cancer, various nano-biological tools, and their advantages over traditional nano-carriers in the treatment of lung cancer. 2. Due to the many applications of nano-biological carriers and nano-biological devices in oncology, they are considered to be important tools for the treatment of cancer in the future. 3. This article has conducted in-depth thinking and exploration on the related investigations, opinions and regulations of overall lung cancer management.

brief introduction
The Mayur Patel group of Nirma University discussed the research progress of nano-bioengineering and nano-technology in the clinical management of lung cancer in recent years. In-depth discussion of bio-nano tools, such as nano-biological carriers and nano-biological devices in the secondary prevention, diagnosis, treatment and therapeutics of lung cancer, and analysis of promising applications of bio-engineering, biomimetic and bionic nano-biological tools.

Graphic guide
I Challenges of current lung cancer management methods
Despite advances in the diagnosis and treatment of lung cancer, lung cancer is still an incurable disease. For decades, chemoprevention and cancer vaccine development have been the objects of oncology research, but they have not been confirmed by clinical evaluations. In addition, imaging and screening technologies have made considerable progress, but current detection technologies cannot diagnose the early stages of the disease. Due to the high diversity of patients, conventional diagnostic methods lack the recognition of molecular/genetic variants of tumor subtypes.
Nanocarrier-based therapy, biological therapy, and immunotherapy have become clinically adjuvant and neoadjuvant therapy for surgery and radiotherapy. With the emergence of new targeted biologics and immunotherapeutics for the treatment of non-small cell lung cancer (NSCLC), treatment outcomes and patient survival rates have improved considerably. However, treatment options for other subtypes of lung cancer such as small cell lung cancer (SCLC) and malignant pleural mesothelioma still need to be improved. Therefore, a deeper understanding of the cellular, genetic, and molecular changes in the occurrence, progression, and metastasis of lung cancer is essential to facilitate the identification of new targets.
The concepts of therapeutic drug monitoring and therapeutic diagnostics are still in their early stages of development and require extensive research. In this case, it is vital to seek bio-nanotechnology to prevent, diagnose and treat lung cancer.
II Nano bioengineering and different types of bio-nano tools
Different bio-nanotechnology derivatives, such as nano-biological carriers and nano-biological devices, have aroused great scientific interest in the treatment of lung cancer. Among them, the biological nanocarriers used in oncology applications can be summarized as: (1) microbial nanosystems and biological nanocarriers (2) cell and cell membrane-derived nanosystems (3) ligand-coupled nanosystems (4) nanobiological devices ,Figure 1.
Figure 1. Biological nanocarriers and nanobiological devices for oncology applications.
Microbial-based nanosystems are gradually being used in clinics. Among them, different microbial nanobiological carriers that have been used to treat malignant tumors include: bacteria, bioengineered bacteria, bacterial microcells, S-membrane-derived nanovesicles, and magnetosomes , Bacterial ghosts, bacterial-derived outer membrane vesicles (proteoliposomes) (OMV), bacterial polymers, bioengineered viruses, bacteriophages and viruses, and fungi and yeasts. Because of the innate nature of microorganisms to specific cells/organs, as well as the advancement of bioomics and bioengineering technology, the carrier potential of microbial nanosystems has been enhanced.
Currently, targeted tumor vectors derived from cells and cell membranes include red blood cells (as shown in Figure 2), white blood cells (WBC), monocytes/macrophages, dendritic cells, neutrophils, lymphocytes, and platelets. , Mesenchymal cells (MSC), cancer cells, extracellular vesicles and exosomes-derived nano-biological carriers. In addition to biomimetic camouflage, cell-based nano-biological carriers also exhibit excellent biocompatibility, multi-molecule and inherent targeting capabilities, self-stealth capabilities, and the ability to integrate host organisms that are beneficial to a variety of tumor applications.


Figure 2. Free-riding treatment of lung B16-F1 metastasis model using red blood cells (RBC).
Conventional nanosystems/nanoparticles are modified to promote tumor targeting through natural, bioengineered, bioinspired or bio-derived biomolecules. In order to effectively target tumors, nano-biocarriers can be one of the following subtypes: conjugate (drug-biopolymer), nano-reservoir (biomolecules used as corona/surface coating) or nano-matrix (Nanosystems are made entirely of biomolecules). Among them, biomolecules include antibodies, lipoproteins, proteins and peptides, lung surfactants and vitamins, etc. Conventional nanocarriers that can be modified by biomolecules include lipid-based nanoparticles, polymer nanoparticles, and the like.
Nano-biological devices are small tools, devices, designs or their components manufactured for various clinical and biomedical applications through bio-nanotechnology. According to the construction materials, nano-biological equipment includes four types based on microorganisms, immunosensors, DNA and tissues.
III Nano-biological carrier for clinical management of lung cancer
Bio-nanotechnology assists in cancer drug discovery and development. In terms of developing targeted therapies, discovering and identifying new cells, biomolecules, and molecular targets, nano-bioengineering tools advance the process of drug discovery and drug development. In addition, nano-biological carriers play an important role in the secondary prevention, diagnosis, treatment and therapeutics of lung cancer.
Through nano-biological carriers, cancer vaccines and immunotherapies are developed. These vaccines and immunotherapies have therapeutic and preventive effects on high-risk patients (malignant tumors). Therefore, nano-biological carriers can be used for secondary prevention of lung cancer. A vaccine based on mannose nanoparticles (as shown in Figure 3) can promote the delivery of dendritic cells and stimulate an immune response against cancer cells.


Figure 3. Vaccine based on mannose-based LCP nanoparticles (MN-LCP-NP) for dendritic cell (DCC) activation.
Through nano-biotechnology, improve the ability of biological imaging and identification of tumor-related molecular markers, and finally realize the nano-biological diagnosis and personalized treatment of lung cancer. Figure 4 has developed a new type of nano-biohybrid to promote multimodal (MRI imaging and micro-PET) imaging of lung cancer.

Figure 4. (i) In vitro and in vivo MRI analysis of Mn2⁺-OCT-PEG-MNPs; (ii) PET analysis12⁴I-labeled Mn2⁺-OCT-PEG-MNPs.
Nano-bioengineering not only helps drug development, but also promotes drug delivery. So far, four generations of nanocarriers have been developed to promote the transformation of tumor therapy from "passive targeting" to "active targeting". Nano-bioengineering and bio-nanotechnology are used in various types of treatments (such as chemotherapy, phototherapy (as shown in Figure 5), immunotherapy, gene/epigenetic therapy (as shown in Figure 6), and radiotherapy (as shown in Figure 7). ), combination therapy and new anti-cancer therapy (as shown in Figure 8)), it has versatility and multi-modal applicability.


Figure 5. PAAO-UCNPs-GOx was developed to enhance the phototherapy of lung cancer.

Figure 6. Nano-biological carriers composed of pH-sensitive lipids have been developed to deliver siRNA that prevents the metastasis and spread of lung cancer.


Figure 7. A nano biological carrier (C@siPLK1-NH) was developed for radiosensitization of non-small cell lung cancer cells (NSCLC).


Figure 8. A nano-biological carrier targeting EGFR has been developed to exert synergistic anti-cancer activity by inducing apoptosis and autophagy.
Nano-biotherapeutics refers to the unified diagnosis and therapeutic application of a single agent. Nano-biotherapeutics currently used include inorganic nanoparticles, nanocages, nanoshells, silica, liposomes, dendrimers, micelles, and other biologically composed metal-organic frameworks. With the advancement of bio-nanotechnology, virus-based and protein-based nano-biological carriers have been used in the treatment and diagnosis of lung cancer.Figure 8. A nano-biological carrier targeting EGFR has been developed to exert synergistic anti-cancer activity by inducing apoptosis and autophagy.
Nano-biotherapeutics refers to the unified diagnosis and therapeutic application of a single agent. Nano-biotherapeutics currently used include inorganic nanoparticles, nanocages, nanoshells, silica, liposomes, dendrimers, micelles, and other biologically composed metal-organic frameworks. With the advancement of bio-nanotechnology, virus-based and protein-based nano-biological carriers have been used in the treatment and diagnosis of lung cancer.
IV Summary and Outlook

With the development of nano-biological science and bio-nanotechnology, obstacles in tumor targeting methods can be greatly overcome, and it has great potential to change the current state of tumor treatment. At present, a large number of different nanotools and new nanosystems have been widely explored to solve various problems faced by traditional therapies and applied to the prevention, diagnosis, treatment and various aspects of tumors (including lung cancer). Bio-nanotechnology tools can use molecular diagnostics and advanced bioimaging technology to design new treatment strategies to enhance tumor treatment. Nano-biological carriers are a useful means to solve tumor heterogeneity through personalized and customized drug delivery. At the same time, the transformational application of nanomedicine is also facing great challenges, and the knowledge integration with interdisciplinary researchers needs to be strengthened. With the development of nano-biological science and bio-nanotechnology, obstacles in tumor targeting methods can be greatly overcome, and it has great potential to change the current state of tumor treatment. At present, a large number of different nanotools and new nanosystems have been widely explored to solve various problems faced by traditional therapies and applied to the prevention, diagnosis, treatment and various aspects of tumors (including lung cancer). Bio-nanotechnology tools can use molecular diagnostics and advanced bioimaging technology to design new treatment strategies to enhance tumor treatment. Nano-biological carriers are a useful means to solve tumor heterogeneity through personalized and customized drug delivery. At the same time, the transformational application of nanomedicine is also facing great challenges, and the knowledge integration with interdisciplinary researchers needs to be strengthened.



Written by: "Nawei Express (English)" Editorial Department
Editor: "Nawei Express (English)" Editorial Department

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