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글로벌화의 확대에 따라 기업의 해외시장진출이 증가하고, 해외직접투자도 증가하고 있다. 우리나라도 최근 10년 사이에 해외직접투자가 2.5배나 증가하였다. 해외직접투자는 시장확대, 수익증대 등 다양한 혜택을 가져오지만, 투자유치국 정부와의 갈등, 투자유치국에서의 국가위험 (또는 정치적위험) 등에 노출되며, 분쟁해결에 어려움이 많다. 해외직접투자에서는 복잡한 법률문제가 발생하고, 다양한 법이 적용된다. 해외직접투자의 법원(source of law)에는 투자유치국의 국내법, 조약(투자보장협정), 국제협약, 국제관습법, 법의 일반원칙, 투자국의 국내법, 제3국의 국내법, 법원판결, 중재판정 등이 있다. 해외직접투자에서의 분쟁은 주로 투자자와 투자유치국 정부간에 발생하는데, 이는 투자자ㆍ국가분쟁해결(ISDS)이 된다. 투자자ㆍ국가분쟁해결(ISDS)은 기업이 상대국 정부를 상대로 법적해결을 하는 것으로 어려움이 많다. 해외투자 관련 협약으로는 체약국과 상대방 체약국 국민간의 투자분쟁해결에 관한 협약(ICSID협약)이 있고, 분쟁해결기구로는 ICSID협약에 근거하여 세계은행(World Bank)이 설립한 국제투자분쟁해결센터(ICSID)가 있다. ICSID는 투자자와 투자유치국 정부와의 분쟁을 중재로 해결한다. 본 논문에서는 해외직접투자에서의 법원(source of law)과 투자자ㆍ국가분쟁해결(ISDS)에 대하여 검토함으로써 해외투자자들이 사전에 관련 법적쟁점을 충분히 검토하여 해외투자를 성공적으로 수행하는데 도움을 주고자 한다.

The development of biomaterials for efficient intracellular delivery of the nucleic acid-based immune-stimulating molecule, CpG oligodeoxynucleotides (CpG), is crucial for their biological activity. In this study, we successfully fabricated polydopamine-coated porous poly(lactic-co-glycolic acid) microparticles (PPM) for the delivery of CpGs. After conjugation of CpGs to PPMs via cleavable disulfide linkages, CpGs were readily released from CpG-conjugated PPM (PPM-s–s-CpGs) in reductive conditions. Released CpGs exhibited significantly enhanced induction of two cytokines, TNF-α and IL-6, in RAW264.7 cells. GpC-conjugated PPMs showed negligible cytokine induction, whereas CpG-conjugated PPMs exhibited strong induction of the two cytokines in RAW264.7 cells. The PPM-s–s-CpGs can serve as immune-stimulating adjuvants to enhance the immune responses of vaccines.

Microspheres (MS; 1-3 μm) with different degrees of surface roughness were prepared to assess the effects of surface topology on internalization into antigen-presenting cells (APCs; macrophages and dendritic cells). In this study, we demonstrated that the intracellular uptake of MS is readily enhanced by surface modification with nanoparticles or cancer cell-derived vesicles (VE) to modulate their surface topology. MS coated with nanovesicles (MS-VE) with high surface roughness was more successfully and efficiently engulfed by APCs, compared with bare MS and those with low surface roughness. Incorporated MPLA within MS-VEs (M/MS-VE) triggered greatly elevated release of immune stimulating cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), from macrophages and dendritic cells, compared to free MPLA. Taken together, this MS-VE could serve as a platform system for the delivery of immune stimulators and antigens to APCs with negligible toxicity.

Recent promising clinical results of RNA therapeutics have drawn big attention of academia and industries to RNA therapeutics and their carrier systems. To improve their feasibility in clinics, systemic evaluations of currently available carrier systems under clinical trials and preclinical studies are needed. In this review, we focus on recent noticeable preclinical studies and clinical results regarding siRNA-based conjugates for clinical translations. Advantages and drawbacks of siRNA-based conjugates are discussed, compared to particle-based delivery systems. Then, representative siRNA-based conjugates with aptamers, peptides, carbohydrates, lipids, polymers, and nanostructured materials are introduced. To improve feasibility of siRNA conjugates in preclinical studies, several considerations for the rational design of siRNA conjugates in terms of cleavability, immune responses, multivalent conjugations, and mechanism of action are also presented. Lastly, we discuss lessons from previous preclinical and clinical studies related to siRNA conjugates and perspectives of their clinical applications.

Polydopamine-coated porous microsphere (PPM) is investigated as a simple and versatile immobilization strategy for immune-stimulating biomolecules to enhance delivery efficiency and immune-stimulating effects such as cytokine induction in macrophages. The PPMs, with diameters of about 2 μm, exhibit simultaneous and efficient incorporation of biomolecules (nucleotides and proteins), which is comparable to that achieved using microspheres carrying biomolecules internally by virtue of their porous structure. Ovalbumin-conjugated PPMs are internalized into macrophages efficiently and selectively via the phagocytic pathway, without any noticeable toxicity. Internalized CpG oligodeoxynucleotide (ODN)-conjugated PPMs (PPM-CpG) greatly enhance the induction of selected cytokines (TNF-α and IL-6) in RAW 264.7 cells compared to that by the soluble CpG ODN and ionic complexes. Therefore, PPMs generated in this study may serve as effective carriers of immune-stimulating biomolecules such as diverse toll-like receptor agonists.